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1.
J Exp Clin Cancer Res ; 43(1): 273, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350223

ABSTRACT

BACKGROUND: The dynamics of mitochondrial respiratory cristae (MRC) and its impact on oxidative phosphorylation (OXPHOS) play a crucial role in driving the progression of high-grade glioma (HGG). However, the underlying mechanism remains unclear. METHODS: In the present study, we employed machine learning-based transmission electron microscopy analysis of 7141 mitochondria from 54 resected glioma patients. Additionally, we conducted bioinformatics analysis and multiplex immunohistochemical (mIHC) staining of clinical glioma microarrays to identify key molecules involved in glioma. Subsequently, we modulated the expression levels of mitochondrial dynamic-1-like protein (DNM1L/DRP1), and its two receptors, mitochondrial fission protein 1 (FIS1) and mitochondrial fission factor (MFF), via lentiviral transfection to further investigate the central role of these molecules in the dynamics of glioblastoma (GBM) cells and glioma stem cells (GSCs). We then evaluated the potential impact of DNM1L/DRP1, FIS1, and MFF on the proliferation and progression of GBM cells and GSCs using a combination of CCK-8 assay, Transwell assay, Wound Healing assay, tumor spheroid formation assay and cell derived xenograft assay employing NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mouse model. Subsequently, we validated the ability of the DNM1L/DRP1-FIS1 axis to remodel MRC structure through mitophagy by utilizing Seahorse XF analysis technology, mitochondrial function detection, MRC abundance detection and monitoring dynamic changes in mitophagy. RESULTS: Our findings revealed that compared to low-grade glioma (LGG), HGG exhibited more integrated MRC structures. Further research revealed that DNM1L/DRP1, FIS1, and MFF played pivotal roles in governing mitochondrial fission and remodeling MRC in HGG. The subsequent validation demonstrated that DNM1L/DRP1 exerts a positive regulatory effect on FIS1, whereas the interaction between MFF and FIS1 demonstrates a competitive inhibition relationship. The down-regulation of the DNM1L/DRP1-FIS1 axis significantly impaired mitophagy, thereby hindering the remodeling of MRC and inhibiting OXPHOS function in glioma, ultimately leading to the inhibition of its aggressive progression. In contrast, MFF exerts a contrasting effect on MRC integrity, OXPHOS activity, and glioma progression. CONCLUSIONS: This study highlights that the DNM1L/DRP1-FIS1 axis stabilizes MRC structures through mitophagy in HGG cells while driving their OXPHOS activity ultimately leading to robust disease progression. The inhibition of the DNM1L/DRP1-FIS1 axis hinders MRC remodeling and suppresses GBM progression. We propose that down-regulation of the DNM1L/DRP1-FIS1 axis could be a potential therapeutic strategy for treating HGG.


Subject(s)
Disease Progression , Dynamins , Glioma , Mitochondria , Mitochondrial Proteins , Humans , Glioma/metabolism , Glioma/pathology , Glioma/genetics , Mice , Animals , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Dynamins/metabolism , Dynamins/genetics , Mitochondria/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Female , Neoplasm Grading , Male , Cell Line, Tumor , Mitochondrial Dynamics , GTP Phosphohydrolases/metabolism , GTP Phosphohydrolases/genetics , Cell Proliferation , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics
2.
World J Gastroenterol ; 30(36): 4057-4070, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39351249

ABSTRACT

BACKGROUND: Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment. This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer. AIM: To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules. METHODS: This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2, PLAU, and CCNA2. The results were validated in an independent dataset. This study also examined the correlations between the model risk score and various clinical features, components of the immune microenvironment, chemotherapeutic drug sensitivity, and metabolism-related pathways. Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines. RESULTS: The prognostic model demonstrated significant predictive value, with the risk score showing a strong correlation with clinical features: It was significantly associated with tumor grade (G) (b P < 0.01), moderately associated with tumor stage (T) (a P < 0.05), and significantly correlated with residual tumor (R) status (b P < 0.01). There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs. Furthermore, the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer. CONCLUSION: The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Pancreatic Neoplasms , Tumor Microenvironment , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/mortality , Humans , Prognosis , Biomarkers, Tumor/genetics , Cell Line, Tumor , Male , Female , Middle Aged , Aged , Tumor Hypoxia/genetics , Predictive Value of Tests , Risk Assessment/methods , Neoplasm Grading , Gene Expression Profiling/methods
3.
World J Urol ; 42(1): 523, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276231

ABSTRACT

PURPOSE: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology. METHODS: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen's Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator. RESULTS: Concordance between biopsy and RP pathology was 0.53 (95CI: 0.43-0.63), 0.38 (95CI: 0.29-0.48), and 0.16 (95CI: 0.11-0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27-0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62-0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11-32), 30% (95CI: 15-44), and 19% (95CI: 7.0-30) in GG 5 for cBx, tBx, or sBx, respectively. CONCLUSION: Overall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment.


Subject(s)
Neoplasm Grading , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Denmark/epidemiology , Middle Aged , Aged , Prostatectomy/methods , Biopsy , Time Factors , Prostate/pathology
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1561-1570, 2024 Aug 20.
Article in Chinese | MEDLINE | ID: mdl-39276052

ABSTRACT

OBJECTIVE: To evaluate the performance of magnetic resonance imaging (MRI) multi-sequence feature imputation and fusion mutual model based on sequence deletion in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). METHODS: We retrospectively collected multi-sequence MR images from 305 glioma patients, including 189 HGG patients and 116 LGG patients. The region of interest (ROI) of T1-weighted images (T1WI), T2-weighted images (T2WI), T2 fluid attenuated inversion recovery (T2_FLAIR) and post-contrast enhancement T1WI (CE_T1WI) were delineated to extract the radiomics features. A mutual-aid model of MRI multi-sequence feature imputation and fusion based on sequence deletion was used for imputation and fusion of the feature matrix with missing data. The discriminative ability of the model was evaluated using 5-fold cross-validation method and by assessing the accuracy, balanced accuracy, area under the ROC curve (AUC), specificity, and sensitivity. The proposed model was quantitatively compared with other non-holonomic multimodal classification models for discriminating HGG and LGG. Class separability experiments were performed on the latent features learned by the proposed feature imputation and fusion methods to observe the classification effect of the samples in twodimensional plane. Convergence experiments were used to verify the feasibility of the model. RESULTS: For differentiation of HGG from LGG with a missing rate of 10%, the proposed model achieved accuracy, balanced accuracy, AUC, specificity, and sensitivity of 0.777, 0.768, 0.826, 0.754 and 0.780, respectively. The fused latent features showed excellent performance in the class separability experiment, and the algorithm could be iterated to convergence with superior classification performance over other methods at the missing rates of 30% and 50%. CONCLUSION: The proposed model has excellent performance in classification task of HGG and LGG and outperforms other non-holonomic multimodal classification models, demonstrating its potential for efficient processing of non-holonomic multimodal data.


Subject(s)
Brain Neoplasms , Glioma , Magnetic Resonance Imaging , Humans , Glioma/diagnostic imaging , Glioma/pathology , Magnetic Resonance Imaging/methods , Retrospective Studies , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Algorithms , Neoplasm Grading , ROC Curve , Sensitivity and Specificity
5.
Tunis Med ; 102(9): 513-520, 2024 Sep 05.
Article in French | MEDLINE | ID: mdl-39287342

ABSTRACT

INTRODUCTION: The grading of glial tumors is based on morphological and sometimes on molecular features. Many markers have been assessed in order to grade the glial tumours without a real consensus. Some authors reported that SRSF1, a spiling factor, presents an expression correlated to the tumours grades. AIM: In this study, we aimed to assess the utility of the SRSF1 into the grading of gliomas based on its immunohistochemical expression. METHODS: The authors conducted a meta-analysis under the PRISMA guidelines during a 10-year-period (2013-2023). The Meta-Disc software 5.4 (free version) was used. Q test and I2 statistics were carried out to explore the heterogeneity among studies. Meta-regression was performed in case of significant heterogeneity. Publication bias was assessed using the funnel plot test and the Egger's test (free version JASP). RESULTS: According to the inclusion criteria, 4 studies from 193 articles were included. The pooled SEN, SPE and DOR accounted respectively for 0.592, 0.565 and 1.852. The AUC was estimated to 0.558 suggesting a bad diagnostic accuracy. The heterogeneity in the pooled SEN and SPE was statistically significant. The meta-regression analysis focusing on the technique used, the clones, the dilution, the interpretation technique revealed no covariate factors (P>0.05). CONCLUSION: Even if this meta-analysis highlighted the absence of a real diagnostic utility of the SRSF1 in grading the glial tumours, the heterogeneity revealed reinforces the need for more prospective studies performed according to the quality assessment criteria.


Subject(s)
Biomarkers, Tumor , Brain Neoplasms , Glioma , Neoplasm Grading , Serine-Arginine Splicing Factors , Humans , Glioma/pathology , Glioma/genetics , Glioma/diagnosis , Glioma/metabolism , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis
6.
Sci Rep ; 14(1): 21680, 2024 09 17.
Article in English | MEDLINE | ID: mdl-39289451

ABSTRACT

Metastasis is the major cause of treatment failure in patients with prostate adenocarcinoma (PRAD). Diverse programmed cell death (PCD) patterns play an important role in tumor metastasis and hold promise as predictive indicators for PRAD metastasis. Using the LASSO Cox regression method, we developed PCD score (PCDS) based on differentially expressed genes (DEGs) associated with PCD. Clinical correlation, external validation, functional enrichment analysis, mutation landscape analysis, tumor immune environment analysis, and immunotherapy analysis were conducted. The role of Prostaglandin D2 Synthase (PTGDS) in PRAD was examined through in vitro experiments, single-cell, and Mendelian randomization (MR) analysis. PCDS is elevated in patients with higher Gleason scores, higher T stage, biochemical recurrence (BCR), and higher prostate-specific antigen (PSA) levels. Individuals with higher PCDS are prone to metastasis, metastasis after BCR, BCR, and castration resistance. Moreover, PRAD patients with low PCDS responded positively to immunotherapy. Random forest analysis and Mendelian randomization analysis identified PTGDS as the top gene associated with PRAD metastasis and in vitro experiments revealed that PTGDS was considerably downregulated in PRAD cells against normal prostate cells. Furthermore, the overexpression of PTGDS was found to suppress the migration, invasion, proliferationof DU145 and LNCaP cells. To sum up, PCDS may be a useful biomarker for forecasting the possibility of metastasis, recurrence, castration resistance, and the efficacy of immunotherapy in PRAD patients. Additionally, PTGDS was identified as a viable therapeutic target for the management of PRAD.


Subject(s)
Adenocarcinoma , Intramolecular Oxidoreductases , Lipocalins , Neoplasm Metastasis , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/metabolism , Intramolecular Oxidoreductases/genetics , Intramolecular Oxidoreductases/metabolism , Lipocalins/genetics , Lipocalins/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Mendelian Randomization Analysis , Neoplasm Grading , Cell Death , Immunotherapy/methods
7.
Turk J Med Sci ; 54(4): 784-791, 2024.
Article in English | MEDLINE | ID: mdl-39295621

ABSTRACT

Background/aim: To investigate the relationship between sex-related visceral obesity and WHO/ISUP nuclear grade in clear cell renal cell carcinoma (ccRCC). Materials and methods: Between January 2018 and June 2022, 95 patients (56 men and 39 women) with pathologically proven ccRCC who underwent abdominal computed tomography examination were retrospectively examined. The patients were classified into two groups: low- and high-WHO/ISUP nuclear grade ccRCC (n = 58 and n = 37), respectively. Patient height, weight, body mass index (BMI), sex, age, subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), and percentage of visceral fat (VF%) were recorded for the two groups. Results: No significant differences were found in age, BMI, SFA, or TFA, but VFA and VF% were significantly higher in the high-grade patient group. In males, maximal tumor diameter (MTD) (67.8% sensitivity and 76.9% specificity) had the highest area under the curve (AUC), while in females, VF% (70.0% sensitivity and 73.7% specificity) had the highest AUC. VF% revealed an odds ratio (OR) of 1.09 in females with high-grade ccRCC, and in males, MTD was an independent predictor of ccRCC with an OR of 1.03. Conclusions: Sex-related body fat tissue, including VFA and VF%, could be used for estimating WHO/ISUP nuclear grade in patients with ccRCC, especially in females.


Subject(s)
Abdominal Fat , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Male , Female , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/diagnostic imaging , Middle Aged , Kidney Neoplasms/pathology , Kidney Neoplasms/diagnostic imaging , Retrospective Studies , Aged , Abdominal Fat/diagnostic imaging , Abdominal Fat/pathology , Sex Factors , Neoplasm Grading , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Adult , Tomography, X-Ray Computed , Body Mass Index
8.
Front Immunol ; 15: 1414716, 2024.
Article in English | MEDLINE | ID: mdl-39315092

ABSTRACT

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. The major clinical challenge includes the asymptomatic state of the disease, making diagnosis possible only at advanced stages. Another OC complication is the high relapse rate and poor prognosis following the standard first-line treatment with platinum-based chemotherapy. At present, numerous clinical trials are being conducted focusing on immunotherapy in OC; nevertheless, there are still no FDA-approved indications. Personalized decision regarding the immunotherapy, including immune checkpoint blockade and immune cell-based immunotherapies, can depend on the effective antigen presentation required for the cytotoxic immune response. The major aim of our study was to uncover tumor-specific transcriptional and epigenetic changes in peripheral blood monocytes in patients with high-grade serous ovarian cancer (HGSOC). Another key point was to elucidate how chemotherapy can reprogram monocytes and how that relates to changes in other immune subpopulations in the blood. To this end, we performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with HGSOC who underwent neoadjuvant chemotherapeutic treatment (NACT) and in treatment-naïve patients. Monocyte cluster was significantly affected by tumor-derived factors as well as by chemotherapeutic treatment. Bioinformatical analysis revealed three distinct monocyte subpopulations within PBMCs based on feature gene expression - CD14.Mn.S100A8.9hi, CD14.Mn.MHC2hi and CD16.Mn subsets. The intriguing result was that NACT induced antigen presentation in monocytes by the transcriptional upregulation of MHC class II molecules, but not by epigenetic changes. Increased MHC class II gene expression was a feature observed across all three monocyte subpopulations after chemotherapy. Our data also demonstrated that chemotherapy inhibited interferon-dependent signaling pathways, but activated some TGFb-related genes. Our results can enable personalized decision regarding the necessity to systemically re-educate immune cells to prime ovarian cancer to respond to anti-cancer therapy or to improve personalized prescription of existing immunotherapy in either combination with chemotherapy or a monotherapy regimen.


Subject(s)
Antigen Presentation , Cystadenocarcinoma, Serous , Monocytes , Ovarian Neoplasms , Humans , Female , Monocytes/immunology , Ovarian Neoplasms/immunology , Ovarian Neoplasms/drug therapy , Antigen Presentation/drug effects , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/immunology , Middle Aged , Neoplasm Grading , Gene Expression Regulation, Neoplastic/drug effects , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy/methods , Epigenesis, Genetic
9.
Cancer Rep (Hoboken) ; 7(9): e2132, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39307946

ABSTRACT

BACKGROUND: Texture analysis derived from computed tomography (CT) may provide clinically relevant imaging biomarkers associated with tumor histopathology. Perihilar cholangiocarcinoma is a malignant disease with an overall poor prognosis. AIMS: The present study sought to elucidate possible associations between texture features derived from CT images with grading, tumor markers, and survival in extrahepatic, perihilar cholangiocarcinomas tumors. METHODS: This retrospective study included 22 patients (10 females, 45%) with a mean age of 71.8 ± 8.7 years. Texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. Survival and clinical parameters were used as primary study outcomes. RESULTS: In discrimination analysis, "S(1,1)SumVarnc" was statistically significantly different between patients with long-term survival and nonlong-term survival (mean 275.8 ± 32.6 vs. 239.7 ± 26.0, p = 0.01). The first-order parameter "skewness" was associated with the tumor marker "carcinoembryonic antigen" (CEA) (r = -0.7, p = 0.01). A statistically significant correlation of the texture parameter "S(5,0)SumVarnc" with tumor grading was identified (r = -0.6, p < 0.01). Several other texture features correlated with tumor markers CA-19-9 and AFP, as well as with T and N stage of tumors. CONCLUSION: Several texture features derived from CT images were associated with tumor characteristics and survival in patients with perihilar cholangiocarcinomas. CT texture features could be used as valuable novel imaging markers in clinical routine.


Subject(s)
Bile Duct Neoplasms , Biomarkers, Tumor , Klatskin Tumor , Neoplasm Grading , Tomography, X-Ray Computed , Humans , Female , Male , Aged , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/mortality , Retrospective Studies , Klatskin Tumor/pathology , Klatskin Tumor/diagnostic imaging , Klatskin Tumor/mortality , Biomarkers, Tumor/analysis , Middle Aged , Aged, 80 and over , Prognosis
10.
Cancer Rep (Hoboken) ; 7(9): e2156, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39307917

ABSTRACT

BACKGROUND: Squamous cell carcinoma of the prostate (SCCP) is a neoplasm that comprises fewer than 1% of all primary prostate cancer diagnoses. Given its rarity, there is a paucity of data regarding the treatment of this disease. The limited literature points to the potential of local therapy in conjunction with chemotherapy to improve patient mortality. METHODS: Using the National Cancer Initiative's Surveillance, Epidemiology, and End Results (SEER) database, a retrospective review of patients diagnosed with primary SCCP between 2000 and 2018 was performed. Patient demographics, tumor characteristics, and patient outcomes based on treatment modality were analyzed. Univariate and survival analyses were conducted with p < 0.05 indicating statistical significance. RESULTS: A total of 66 patients were identified. Five-year overall survival (5y OS) was 24%; mean and median survival were 2.2 years (1.8, 2.7) and 1.2 years (0.3, 2.1), respectively. Patients with Grade I or Grade II disease had an increased 5y OS of 55% (27%, 83%). In comparison, 5y OS was 13% (-2%, 29%) for patients with Grade III and Grade IV disease (p = 0.017). Analysis of 5y OS based on disease histology revealed patients with papillary SCC had a 5y OS of 50% [9.2%, 91%], compared to 21% [9%, 34%] for patients with SCC, not otherwise specified and 0% for those with lymphoepithelial carcinoma (p = 0.048). Analysis of 5y OS stratified by treatment modality revealed no statistically significant change with any treatment (surgery, radiotherapy, and chemotherapy). No difference in 5y OS was seen between those treated with radical prostatectomy versus external beam radiation therapy. CONCLUSIONS: The literature on SCCP remains sparse; the rarity of this disease limits analysis. While the investigation undertaken in this paper does not find any change in 5y OS regardless of treatment modality, the variation in 5y OS based on histologic classification of SCCP points to a potential route for the future treatment of this disease.


Subject(s)
Carcinoma, Squamous Cell , Prostatic Neoplasms , SEER Program , Humans , Male , Aged , Retrospective Studies , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/mortality , Middle Aged , SEER Program/statistics & numerical data , Prostatectomy/statistics & numerical data , Treatment Outcome , Survival Rate , Neoplasm Grading , Aged, 80 and over , Prostate/pathology
11.
Chin Clin Oncol ; 13(Suppl 1): AB011, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39295329

ABSTRACT

BACKGROUND: World Health Organization (WHO) grade 4 astrocytoma is a high-grade brain tumour in adults. Tumour treating fields (TTF) has been shown to improve overall survival (OS). Few studies have explored quality-of-life (QoL) in these patients. This study aims to assess the QoL of TTF patients and OS. METHODS: This was a prospective multicenter study of adult patients diagnosed with WHO grade 4 astrocytoma from 2018 to 2023 receiving TTF for >1 month after completing standard therapy. A propensity-score matched comparison with a 1:2 ratio with historical control was performed for OS analysis. The patients completed European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30/BN20 questionnaires before TTF and at 3-month interval. Primary outcomes included OS, and secondary outcomes included QoL and TTF-associated adverse effects at 3 months. RESULTS: A total of 141 patients were reviewed, with TTF patients (n=47, 33%) and propensity-score matched controls (n=94). The mean duration of TTF use was 10±8 months. The mean age of the TTF group was 54±13 years, and for the control group 52±13 years. Sixty percent (n=28) were male, similar to the control group with 71% (n=67) (P=0.16). Seventy-two percent of TTF patients had preoperative Karnofsky Performance Scale (KPS) score ≥80, while controls had 70% (P=0.79). Five (11%) TTF patients and 8 (9%) controls were IDH1 mutant (P=0.70). Twenty (43%) TTF patients and 42 (45%) controls were O6-methylguanine-DNA methyltransferase promoter (pMGMT) methylated (P=0.81). Twenty-one (45%) of TTF patients and 55 (59%) of controls had gross total resection (P=0.72). After adjusting for independent predictors for OS, the median OS of the TTF group was 22.4 months [interquartile range (IQR): 18.6-26.5 months], significantly longer than the control group (17.2 months; IQR: 12.1-22.3 months) (log-rank test: P=0.01). Forty-seven TTF patients and 40 control patients completed EORTC questionnaires. There was no difference for EORTC functional and symptom scores between the TTF and control group [P=0.45, analysis of variance (ANOVA)] at 3 months. Thirty-two (67%) of TTF patients reported associated RTOG grade I scalp dermatitis. CONCLUSIONS: TTF for WHO grade 4 astrocytoma patients is an independent predictor for OS. QoL between the groups was similar, and overall QoL over time for TTF patients was not affected. TTF is a novel and effective outpatient treatment with minimal adverse effects.


Subject(s)
Astrocytoma , Propensity Score , Quality of Life , Humans , Male , Astrocytoma/therapy , Astrocytoma/mortality , Female , Prospective Studies , Middle Aged , Adult , Neoplasm Grading , Brain Neoplasms/therapy , Aged , World Health Organization
12.
Chin Clin Oncol ; 13(Suppl 1): AB010, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39295328

ABSTRACT

BACKGROUND: Anaplastic astrocytoma [AA; World Health Organization (WHO) grade III] is a diffusely infiltrative astrocytic brain tumor with anaplasia and represents 3.3% of primary brain tumors. Overall, 5-year median survival can range from 22% to 50%, depending on various prognostic features, including the patient's age, tumor location and genetics, resection, etc. Given the higher grade and increased likelihood of transformation to WHO-grade IV tumors (glioblastomas), these tumors are generally treated aggressively upfront. Headache and seizures are the most common symptoms, occurring in about 50% of the cases. Other symptoms, including memory loss, motor weakness, language deficit, and cognitive and personality changes, occur in 20% of cases. Standard treatment involves surgical resection, radiotherapy, and chemotherapy, but treatment options are greatly limited for progression and recurrence. This paper highlights the case of a 48-year-old male who presents with chronic progressive cephalgia and a new-onset seizure. We review the diagnostic and therapeutic challenges associated with the treatment of AA. CASE DESCRIPTION: We describe a patient who presented with chronic progressive cephalgia, gradual right-sided weakness, an asymmetrical face, slurred speech, and a new-onset focal-to-bilateral seizure. A cranial magnetic resonance imaging revealed a mass in the left frontoparietal region, causing herniation of the cerebri to the right. The patient had a maximal tumor resection, and the histopathology showed tissue sections containing tumors that were infiltrative in the stroma, forming a diffuse pattern consisting of proliferation of oval, round, polygonal, spindle, pleomorphic oval nucleated cells, hyperchromatic, some nucleoli appearing prominent, and cytoplasmaeosinophilic. There were areas of stromal necrosis and mitosis [3/10 high power field (HPF)]. The pathology result was reported with AA. The patient underwent concomitant chemoradiation and followed oral chemotherapy with temozolomid. Subsequent imaging revealed a significant decrease in the tumor's size and a resolution of the compression of the brain parenchyma underneath. The Response Assessment in Neuro-Oncology (RANO) evaluation showed partial responses with good clinical improvement. CONCLUSIONS: The case presented an AA that was responsive to radiotherapy and temozolomid chemotherapy. Despite being rare, knowledge of this malignant tumor type and a multidisciplinary approach to case management are essential to optimizing treatment results.


Subject(s)
Astrocytoma , Humans , Male , Astrocytoma/therapy , Astrocytoma/complications , Astrocytoma/pathology , Middle Aged , Brain Neoplasms/therapy , Brain Neoplasms/complications , Brain Neoplasms/pathology , World Health Organization , Neoplasm Grading
13.
Chin Clin Oncol ; 13(Suppl 1): AB055, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39295373

ABSTRACT

BACKGROUND: Infantile high-grade glioma (IHG) is diagnosed in patients less than 12 months of age. Studies have shown that it displays a more stable genome and is usually single mutation-driven. The most identifiable mutations are receptor tyrosine kinase (RTK) fusion, such as neurotrophic tyrosine receptor kinase (NTRK) family, reactive oxygen species (ROS1), anaplastic lymphoma kinase (ALK), and mesenchymal-epithelial transition (MET) factor. The current principal treatment remains to be surgery, but it is challenging for a complete resection due to hemispheric involvement. Use of chemotherapeutic drugs for IHG is still under debate, with targeted therapy showing efficacy in promoting tumor shrinkage. Despite being a challenging central nervous system (CNS) tumor, the overall survival of IHG is superior to other high-grade gliomas. CASE DESCRIPTION: This is a retrospective review of local IHG patients and their outcome. Up till the end of 2022, we identified eight IHG patients in our local data. Mean age of diagnosis was 3 months. There were four males and four females. Seven patients had histological diagnosis of glioblastoma and one patient had a diagnosis of anaplastic astrocytoma. One patient had her tumor located in the infratentorial region. Four patients had multilobar involvement. NTRK fusion was found in four patients (ETV6-NTRK3 fusion and TPR-NTRK1 fusion). ALK fusion was found in one patient (HMBOX1-ALK). ROS1 fusion was found in one patient (ZCCHZ8-ROS1). All patients underwent chemotherapy, with four patients switched to NTRK inhibitors and one patient to ROS1 inhibitors afterward. Surgery was performed at various time points for these patients. Two patients passed away, at 22 and 35 months of age at submission of this abstract. CONCLUSIONS: Infantile high-grade glioma should be regarded as a unique tumor entity and a multidisciplinary approach is paramount in improving survival for this group of patients.


Subject(s)
Glioma , Humans , Male , Female , Glioma/pathology , Infant , Retrospective Studies , Hong Kong , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Neoplasm Grading
14.
Chin Clin Oncol ; 13(Suppl 1): AB094, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39295412

ABSTRACT

BACKGROUND: Glioma is the second most common type of brain tumor, representing 24% of all brain tumor cases. The role of body mass index (BMI) on glioma remains unclear, with conflicting findings regarding the association between higher BMI and the risk of developing certain brain tumors. Glioblastoma, an aggressive and malignant form of glioma with limited treatment options and a poor prognosis, has been linked to BMI in some studies, suggesting that individuals with higher BMIs may have an elevated risk of glioblastoma development. However, a comprehensive understanding of the mechanisms underlying this relationship and its extent is still needed. The study aimed to investigate the correlation between BMI and the grading and survival of glioma patients. METHODS: A retrospective cross-sectional analysis was conducted on 117 histologically confirmed glioma patients at Dr. Sardjito General Hospital in Yogyakarta, Indonesia. Clinical data were collected from medical records. BMI was calculated by measuring weights (kg) and dividing it by squared heights (m2). The statistical analysis focused on assessing the association between BMI, tumor grade, and patient survival. RESULTS: Among 117 glioma patients, glioblastoma was the most prevalent tumor type (48.7%; n=57/117), followed by diffuse astrocytoma (22%; n=26/117). The remaining cases included anaplastic ependymoma, anaplastic oligodendroglioma, and pilocytic astrocytoma. Most patients were male (61%), with an average age of 47.5 years, age ranges between 20 and 79 years. The majority had grade IV of World Health Organization (WHO) classification (58%, n=68/117), while only two patients were classified as grade I. The average BMI was 23.5 kg/m2, indicating overweight status for the Asian population, with more than half of the patients being overweight or obese (54%, n=63/117). Additionally, ten patients were underweight. There was a trend of higher BMI being associated with higher grading and survival. However, no significant association between BMI and tumor grade (P=0.23) or survival (P=0.26) was found. CONCLUSIONS: Although no significant associations were found between BMI, tumor grade, and survival in glioma patients, further studies are warranted. The high prevalence of overweight and obesity among patients should be further investigated to provide valuable insights for patient management and care.


Subject(s)
Body Mass Index , Brain Neoplasms , Glioma , Neoplasm Grading , Humans , Male , Glioma/complications , Glioma/mortality , Female , Retrospective Studies , Cross-Sectional Studies , Middle Aged , Adult , Brain Neoplasms/complications , Brain Neoplasms/mortality , Neoplasm Grading/methods , Aged , Young Adult , Prognosis
15.
Chin Clin Oncol ; 13(Suppl 1): AB003, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39295416

ABSTRACT

BACKGROUND: We are primarily investigating the prognostic role of cell-cycle-dependent kinase inhibitor (CDKN)-2A homozygous deletion in central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas. Additionally, traditional prognostic factors for grade 4 gliomas will be examined, and our results will be validated. METHODS: We conducted a retrospective analysis of glioma cohorts in our institute. Medical records were reviewed for 142 glioblastoma patients for 15 years, and pathological slides were examined again for the updated diagnosis according to the 2021 WHO classification of CNS tumors. The isocitrate dehydrase (IDH) mutation and CDKN2A deletion were examined by next generation sequencing (NGS) analysis using ONCO accuPanel®. Traditional prognostic factors including age, WHO performance status, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation were examined. RESULTS: After the exclusion of 6 patients with poor status of pathologic samples, 136 glioblastoma that were diagnosed by previous WHO criteria were changed into 29 (21.3%) astrocytoma, IDH-mutant, CNS WHO grade 4 and 107 (78.7%) glioblastoma, IDH-wildtype, CNS WHO grade 4. Among them, 61 patients (56.0%) had CDKN2A deletion. Group A with IDH-wildtype and CDKN2A deletion had a mean overall survival (OS) of 15.70 months [95% confident interval (CI): 13.86-17.54], group B with IDH-mutant and CDKN2A deletion had a mean OS of 19.37 months (95% CI: 13.43-25.30), group C with IDH-wildtype and intact CDKN2A had a mean OS of 22.63 months (95% CI: 20.10-25.17), and group D with IDH-mutant and intact CDKN2A had a mean OS of 33.38 months (95% CI: 29.35-37.40). Multifactor analysis showed following factors were independently associated with OS: age [≥50 vs. <50 years; hazard ratio (HR) 4.642], extent of resection (gross total resection vs. others; HR 5.523), WHO performance (0, 1 vs. 2; HR 5.007), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.075), IDH mutation (mutant vs. wildtype; HR 6.358), and CDKN2A deletion (absence vs. presence; HR 13.452). CONCLUSIONS: The presenting study suggests that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low-grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcomes due to CDKN2A deletion.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Glioma , Isocitrate Dehydrogenase , Mutation , Humans , Glioma/genetics , Glioma/pathology , Male , Female , Middle Aged , Isocitrate Dehydrogenase/genetics , Retrospective Studies , Cyclin-Dependent Kinase Inhibitor p16/genetics , Adult , World Health Organization , Neoplasm Grading , Aged , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Homozygote , Gene Deletion , Young Adult
16.
Cells ; 13(17)2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39273062

ABSTRACT

Primary central nervous system tumors are the most frequent solid tumors in children, accounting for over 40% of all childhood brain tumor deaths, specifically high-grade gliomas. Compared with pediatric low-grade gliomas (pLGGs), pediatric high-grade gliomas (pHGGs) have an abysmal survival rate. The WHO CNS classification identifies four subtypes of pHGGs, including Grade 4 Diffuse midline glioma H3K27-altered, Grade 4 Diffuse hemispheric gliomas H3-G34-mutant, Grade 4 pediatric-type high-grade glioma H3-wildtype and IDH-wildtype, and infant-type hemispheric gliomas. In recent years, we have seen promising advancements in treatment strategies for pediatric high-grade gliomas, including immunotherapy, CAR-T cell therapy, and vaccine approaches, which are currently undergoing clinical trials. These therapies are underscored by the integration of molecular features that further stratify HGG subtypes. Herein, we will discuss the molecular features of pediatric high-grade gliomas and the evolving landscape for treating these challenging tumors.


Subject(s)
Brain Neoplasms , Glioma , Humans , Glioma/pathology , Glioma/therapy , Glioma/genetics , Child , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Brain Neoplasms/genetics , Neoplasm Grading , Immunotherapy/methods
17.
J Ovarian Res ; 17(1): 192, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39342316

ABSTRACT

BACKGROUND: High grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in which patients have still yet to respond meaningfully to clinically available immunotherapies. Hence, novel immune targets are urgently needed. Our past work has identified that mast cells are significantly upregulated at the mRNA level in HGSOC patient tumors following neoadjuvant chemotherapy (NACT) exposure. Therefore, in this current investigation we sought to characterize intratumoral mast cell phenotypic changes as a result of NACT exposure and determine how these adaptations are associated with patient clinical outcomes. METHODS: Hematologic immunohistochemistry was employed to determine mast cell levels in 36 matched pre- and post-NACT HGSOC patient tumors. Fluorescent Immunohistochemistry was utilized to identify Tryptase+(carboxypeptidase A3 (CPA3) + mast cells as well as histamine levels in 29 and 20, respectively, matched pre- and post-NACT HGSOC patient tumors. Finally, human immortalized mast cells, LUVA were stimulated with carboplatin and paclitaxel and genomic changes were analyzed by quantitative PCR. RESULTS: Hematologic labeled intratumoral mast cells were significantly upregulated in the intraepithelial and stromal regions of the tumor, post-NACT. Lower levels of pre-NACT mast cells were significantly associated with an improved progression-free survival (PFS). Histamine, a marker of mast cell degranulation was similarly upregulated in post-NACT exposed tumors. Through the characterization of mast cell specific proteases Tryptase and CPA3, it was found that Tryptase+/ CPA3 + mast cells were significantly upregulated both in the intraepithelial and stromal compartments of the tumor, while Tryptase + cells were significantly upregulated in the stromal regions of the tumor. Lower post-NACT treated levels with Tryptase+/ CPA3 + cells were significantly associated with improved overall survival (OS) and PFS while higher Tryptase + mast cells were associated with improved OS. Finally, following chemotherapy exposure mast cell activating factors AREG and CCL2 were significantly upregulated while TGFB1, an inhibitor of mast cell activation was downregulated in LUVA cells. CONCLUSIONS: Enhanced mast cell numbers, as well as activation and degranulation are a consequence of NACT exposure. Post-NACT mast cells displayed differing associations with survival outcomes that was dependent upon granule classification. Ultimately, mast cells represent a clinically relevant putative HGSOC immune target.


Subject(s)
Mast Cells , Neoadjuvant Therapy , Ovarian Neoplasms , Humans , Female , Mast Cells/drug effects , Mast Cells/metabolism , Neoadjuvant Therapy/methods , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/genetics , Middle Aged , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/genetics , Aged , Phenotype , Neoplasm Grading , Histamine/metabolism , Tryptases/metabolism , Tryptases/genetics
18.
J Orthop Surg Res ; 19(1): 607, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39342379

ABSTRACT

PURPOSE: This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. METHODS: A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. RESULTS: Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19-53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13-72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6-12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). CONCLUSIONS: Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. LEVEL OF EVIDENCE: level IV Therapeutic.


Subject(s)
Arthrodesis , Bone Neoplasms , Denosumab , Giant Cell Tumor of Bone , Neoplasm Recurrence, Local , Radius , Humans , Female , Denosumab/therapeutic use , Male , Giant Cell Tumor of Bone/surgery , Giant Cell Tumor of Bone/drug therapy , Giant Cell Tumor of Bone/diagnostic imaging , Radius/surgery , Radius/diagnostic imaging , Adult , Retrospective Studies , Arthrodesis/methods , Bone Neoplasms/surgery , Bone Neoplasms/drug therapy , Young Adult , Middle Aged , Treatment Outcome , Combined Modality Therapy , Follow-Up Studies , Bone Density Conservation Agents/therapeutic use , Bone Density Conservation Agents/administration & dosage , Neoplasm Grading , Bone Transplantation/methods
19.
Asian Pac J Cancer Prev ; 25(9): 3143-3149, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39342593

ABSTRACT

OBJECTIVE: The aim of this study was to analyze the expression of Snail in the colorectal adenocarcinoma. METHODS: This study used a cross-sectional design. Seventy four paraffin embedded block of Colorectal Adenocarcinoma were assessed using Snail rabbit polyclonal antibody and their expression were performed using Olympus CX-43 light microscope. The relationship between Snail expression with histopathological grading, tumor budding grading, lymphovascular invasion and metastases of colorectal adenocarcinoma ability were statistically analyzed by Mann Whitney tests and presented in tables using SPSS 27. RESULT: From 74 samples examined, in samples with low grade tumor budding (n=11), there were 9 samples (81.8%) with weak expression, while those with strong expression were 2 samples (18.2%). In samples with intermediate grade tumor budding (n=28), there were 17 samples (60.7%) with weak expression, while those with strong expression were 11 samples (39.3%). In samples with high grade tumor budding (n=35), there were 13 samples (37.1%) with weak expression, while those with strong expression were 22 samples (62.9%). In samples with lymphovascular invasion (n=14), there were 10 samples (71.4%) with strong expression, while those with weak expression were 4 samples (28.6%). In samples with metastases (n=23), there were 16 samples (69.6%) with strong expression, while those with weak expression were 7 samples (30.4%). There was a significant relationship between the expression of Snail with tumor budding grade (p=0.003), lymphovascular invasion and metastases (p=<0.001), but there was no significant relationship with histopathological grade (p=0.942). CONCLUSION: The Snail expression can be used as a prognostic factor in colorectal adenocarcinoma.


Subject(s)
Adenocarcinoma , Biomarkers, Tumor , Colorectal Neoplasms , Snail Family Transcription Factors , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Snail Family Transcription Factors/metabolism , Adenocarcinoma/pathology , Adenocarcinoma/metabolism , Prognosis , Male , Female , Biomarkers, Tumor/metabolism , Middle Aged , Cross-Sectional Studies , Aged , Follow-Up Studies , Neoplasm Invasiveness , Lymphatic Metastasis , Adult , Neoplasm Grading , Aged, 80 and over
20.
Int J Mol Sci ; 25(18)2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39337607

ABSTRACT

PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5'tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5'-tRNA-Glu-TTC-9-1_L30 and 5'-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score ≥ 7 and staging disease beyond IIA, supporting that the 5'tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5'tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.


Subject(s)
Biomarkers, Tumor , Extracellular Vesicles , Prostate-Specific Antigen , Prostatic Neoplasms , Semen , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Prostate-Specific Antigen/blood , Semen/metabolism , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Middle Aged , Aged , RNA, Transfer/genetics , Neoplasm Grading
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