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Background: Patients with gastric cancer (GC) who underwent radical surgery require long-term follow-up (usually 5 years). The purpose of this study was to explore individualized follow-up strategies for patients with GC. Methods: This is a retrospective cohort study that established a clinicopathologic database of patients who underwent gastrectomy from January 2010 to December 2020 at Ningbo No. 2 Hospital. Follow-up was performed until March 2023. The rate of new-onset recurrence of patients with GC was explored annually according to different pTNM stages, defining a recurrence rate of less than 1% as adequate follow-up time. Results: Of the 1606 patients who were eligible, the total number of patients who completed the 5- and 10-year follow-up was 1107 and 586, respectively. A total of 444 cases were diagnosed with recurrence. The recurrence rate for stage IA patients was consistently less than 1% during the follow-up time. The adequate follow-up time (the rate of new-onset recurrence less than 1%) was 5 years for stage IB and IIA patients, and 8 years for stage IIB and IIIA patients, respectively. In contrast, stage IIIB patients were always at risk of recurrence during the follow-up time (>1%). Time to a new recurrence rate for stage IIIC patients was 6 years. Conclusion: Among patients who underwent radical gastrectomy, the rate of new-onset recurrence varied among patients with different pTNM stages. This study suggests that the follow-up of GC can be individualized and refer to pTNM stage.
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PURPOSE: To analyze the presentation and outcomes of eyelid and periocular sebaceous gland carcinoma (SGC) based on prognostic stage of the 8th edition of American Joint Committee on Cancer (AJCC) classification. DESIGN: Retrospective clinical cohort study METHODS: ⢠Setting: Quaternary referral center ⢠Study population: 500 eyes of 499 patients with SGC ⢠Intervention: Excisional biopsy, chemotherapy, Orbital exenteration ⢠Main outcome measures: Tumor recurrence, lymph node metastasis, systemic metastasis, and death based on AJCC prognostic staging RESULTS: The mean age at presentation with SGC was 57 years (55 years; range, 26 to 82 years). Based on the 8th edition of AJCC classification, tumors belonged to Stage 0 (n=13, 3%), I (n=158, 32%), II (n=269, 54%), III (n=48, 9%), and IV (n=12, 2%). At a mean follow-up of 26 months (median, 10 months; range, <1 to 192 months), tumor recurrence, lymph node metastasis, systemic metastasis, and disease-related death were seen in 39 (10%), 65 (16%), 33 (8%), and 33 (8%) patients respectively. Tumor recurrence rates did not differ significantly between the stages (p=0.472). The 5-year Kaplan-Meier estimates of regional lymph node metastasis, systemic metastasis, and metastasis-related death were higher for stage II (12%, 11%, and 12%, respectively), III (69%, 25%, and 42%, respectively) and IV (70%, 100%, and 100%, respectively) compared to stage I (0%, 6%, and 6%, respectively). Cox proportional analysis revealed a greater hazard ratio (HR) for lymph node metastasis in stage II (HR, 3.498; 95% CI, 0.200 to 10.200; p<0.022), III (HR, 95% CI, 24.836; 8.733 to 70.631; p<0.001), and IV (HR, 53.731; 95% CI, 15.418 to 187.253; p<0.001), systemic metastasis in stage III (HR. 13.895; 95% CI, 3.871 to 49.874; p<0.001) and IV (HR, 81.465; 95% CI, 22.267 to 298.051; p<0.001) and for disease-related death in stage III (HR, 9.182; 95% CI, 2.743 to 30.728; p<0.001) and IV (HR, 85.237; 95% CI, 25.331 to 287.422; p<0.001), compared to stage I. CONCLUSION: The prognostic staging of the 8th edition AJCC classification predicts the prognosis of patients with eyelid and periocular SGC, which worsens with the advancing stage. The high incidence of lymph node and systemic metastasis accounts for mortality in these patients.
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The prognostic significance of tumor size in T3b differentiated thyroid cancer (DTC) remains debated and underexplored. This study aimed to examine the varying impact of T3b based on tumor size, analyzing disease-specific survival, disease-free survival, and overall survival. A retrospective review of 6282 DTC patients who underwent thyroid surgery at Seoul St. Mary's Hospital from September 2000 to December 2017 was conducted. T3b was classified into three subcategories, T3b-1 (≤2 cm), T3b-2 (2-4 cm), and T3b-3 (>4 cm), using the same size criteria for T1, T2, and T3a. T3b-1 showed no significant difference in disease specific survival compared to T1, and both disease-free and disease-specific survival curves were sequentially ranked as T1, T3b-1, T2, T3a, T3b-2, and T3b-3. The modified T category, reclassifying T3b-1 as T1, demonstrated superior staging performance compared to the classic T category (c-index: 0.8961 vs. 0.8959 and AUC: 0.8573 vs. 0.8518). Tumors measuring 2 cm or less within the T3b category may require downstaging, and a modified T category could improve the precision of prognostic staging compared to the current T category.
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BACKGROUND: The eighth edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single-N and multiple-N descriptors. RESEARCH QUESTION: Do the single-N and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? STUDY DESIGN AND METHODS: Using the National Cancer Database, we analyzed patients with pathologically staged N1 and N2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pathological single N2 (pSingle-N2), and pathological multiple N2 (pMulti-N2). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox regression models. RESULTS: In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 patients with NSCLC demonstrated pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2 disease, respectively. Patients with pMulti-N1 and pMulti-N2 disease showed a shorter survival than those with pSingle-N1 and pSingle-N2 disease, respectively (hazard ratio [HR], 1.22 [P < .0001] for N1 and 1.39 [P < .0001] for N2). After adjusting age, sex, and histologic findings, the HR for pSingle-N2 compared with pMulti-N1 disease was 1.05 (P = .0031). Patients with pN1 disease were categorized by metastatic lymph node count (1, 2, 3, ≥ 4), showing significant prognostic differences among groups (P < .0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy, or more; survival ≥ 30 days; ≥ 10 examined lymph nodes; and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708), analyses supported these results. INTERPRETATION: Patients with NSCLC with one metastatic lymph node, whether in N1 or N2 stations, showed better survival than those with more than one lymph node involved. Patients with NSCLC with a single-skip N2 lymph node metastasis showed survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to four or more was sequentially prognostic.
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OBJECTIVE: Examining the distribution of breast cancer (BC) stage and molecular subtype among women aged below (< 45 years), within (45-65 years), and above (> 65 years) the recommended screening age range helps to understand the screening program's characteristics and contributes to enhancing the effectiveness of BC screening programs. METHODS: In this retrospective study, female patients with newly diagnosed BC from 2010 to 2020 were identified. The distribution of cases in terms of TNM stages, severity classes, and subtypes was analysed according to age groups. RESULTS: A total of 3282 women diagnosed with BC were included in the analysis. Among these cases 51.4% were detected outside the screening age group, and these were characterized by a higher TNM stage compared to those diagnosed within the screening age band. We observed significantly higher relative frequency of advanced BC in the older age group compared to both the screening age population and women younger than 45 years (14.9% vs. 8.7% and 7.7%, P < 0.001). HR-/HER2- and HER+ tumours were relatively more frequent among women under age 45 years (HR-/HER2-: 23.6%, HER2+: 20.5%) compared to those within the screening age range (HR-/HER2-: 13.4%, HER2+: 13.9%) and the older age group (HR-/HER2-: 10.4%, HER2+: 11.5%). CONCLUSIONS: The findings of our study shed light on potential areas for the improvement of BC screening programs (e.g., extending screening age group, adjusting screening frequency based on molecular subtype risk status) in Hungary and internationally, as well.
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PURPOSE: This study aims to develop a novel prediction model and risk stratification system that could accurately predict progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC). METHODS: Herein, we included 106 individuals diagnosed with NPC, who underwent 18F-FDG PET/CT scanning before treatment. They were divided into training (n = 76) and validation (n = 30) sets. The prediction model was constructed based on multivariate Cox regression analysis results and its predictive performance was evaluated. Risk factor stratification was performed based on the nomogram scores of each case, and Kaplan-Meier curves were used to evaluate the model's discriminative ability for high- and low-risk groups. RESULTS: Multivariate Cox regression analysis showed that N stage, M stage, SUVmax, MTV, HI, and SIRI were independent factors affecting the prognosis of patients with NPC. In the training set, the model considerably outperformed the TNM stage in predicting PFS (AUCs of 0.931 vs. 0.841, 0.892 vs. 0.785, and 0.892 vs. 0.804 at 1-3 years, respectively). The calibration plots showed good agreement between actual observations and model predictions. The DCA curves further justified the effectiveness of the model in clinical practice. Between high- and low-risk group, 3-year PFS rates were significantly different (high- vs. low-risk group: 62.8% vs. 9.8%, p < 0.001). Adjuvant chemotherapy was also effective for prolonging survival in high-risk patients (p = 0.009). CONCLUSION: Herein, a novel prediction model was successfully developed and validated to improve the accuracy of prognostic prediction for patients with NPC, with the aim of facilitating personalized treatment.
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PURPOSE: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. METHODS: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. RESULTS: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. CONCLUSION: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging.
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Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Organometallic Compounds , Positron Emission Tomography Computed Tomography , Humans , Positron Emission Tomography Computed Tomography/methods , Female , Male , Middle Aged , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Carcinoma/diagnostic imaging , Prospective Studies , Adult , Aged , Neoplasm Staging , Gallium Radioisotopes , Radiopharmaceuticals , Gallium IsotopesABSTRACT
BACKGROUND: The first COVID-19 wave in 2020 necessitated temporary suspension of non-essential medical services including organized cancer screening programs in Belgium. This study assessed the impact of the pandemic on breast cancer (BC) incidence, stage at diagnosis, and management in Belgium in 2020. METHODS: All Belgian residents diagnosed with in situ or invasive BC in 2015-2020 in the nationwide, population-based cancer registry database were included. Incidence trends for 2015-2019 were extrapolated to predict incidence and stage distribution for 2020 and compared with the observed values. National healthcare reimbursement data were used to examine treatment strategies. Exact tumor diameter and nodal involvement, extracted from pathology reports, were analyzed for 2019 and 2020. RESULTS: 74,975 tumors were selected for analysis of incidence and clinical stage. Invasive BC incidence declined by -5.0% in 2020, with a drop during the first COVID-19 wave (Mar-Jun; -23%) followed by a rebound (Jul-Dec; +7%). Predicted and observed incidence (in situ + invasive) was not different in patients < 50 years. In the 50-69 and 70 + age groups, significant declines of -4.1% and - 8.4% respectively were found. Excess declines were seen in clinical stage 0 and I in Mar-Jun, without excess increases in clinical stage II-IV tumors in Jul-Dec. There was no increase in average tumor diameter or nodal involvement in 2020. Patients diagnosed in Mar-Jun received significantly more neoadjuvant therapy, particularly neoadjuvant hormonal therapy for patients with clinical stage I-II BC. CONCLUSIONS: BC incidence decline in 2020 in Belgium was largely restricted to very early-stage BC and patients aged 50 and over. Delayed diagnosis did not result in an overall progression to higher stage at diagnosis in 2020. Observed treatment adaptations in Belgium were successful in prioritizing patients for surgery while preventing tumor progression in those with surgical delay. Continuation of monitoring BC incidence and stage in the future is crucial.
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Background Breast carcinoma has been the most prevalent cancer in women, with research-based evidence showing a significant rise in the incidence of cancer and related morbidity and mortality in the Indian subcontinent. The predictive value of plasmatic lactate dehydrogenase (LDH) levels has been studied in breast cancer. Numerous studies have connected high LDH values to a poor prognosis, increased risk of incidence, recurrence, and associated mortality in patients with breast carcinoma. This study aimed to assess the clinical profile of breast carcinoma and determine the correlation of serum lactate dehydrogenase levels with the stage of the disease and assessment of high-risk features using histopathology and immunohistochemistry. Methods A total of 75 patients with carcinoma breast were enrolled for this study and classified into two groups: upfront surgery and post-adjuvant therapy. Serum LDH levels were estimated a day before the surgery (baseline) and on postoperative days 1, 7, 14, and 30. The clinical tumor, node, metastasis (cTNM) staging was correlated with pathological tumor, node, metastasis TNM (pTNM) staging and immunohistochemistry findings. Results The clinical characteristics of breast cancer, serum LDH levels, and stage of the disease were collected and analyzed. A significant decreasing trend was noted in LDH values post-op days, and statistically significant higher LDH values were noted in the triple-negative group, positive lymph nodes, and positive lymphovascular invasion patients. Conclusion Regularly elevated levels or an unanticipated rise in serum LDH might indicate poor outcomes. Hence, this non-specific enzyme marker can be suggested to be used routinely to assess disease outcomes.
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BACKGROUND: The aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer. METHODS: 1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected. RESULTS: Serum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage. CONCLUSIONS: The serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.
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Stomach Neoplasms , Humans , Male , Cholesterol, LDL , Case-Control Studies , Lipid Metabolism , Triglycerides , Biomarkers , Cholesterol, HDLABSTRACT
Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy.
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This study aims to decipher crucial biomarkers regulated by p73 for the early detection of colorectal cancer (CRC) by employing a combination of integrative bioinformatics and expression profiling techniques. The transcriptome profile of HCT116 cell line p53 - / - p73 + / + and p53 - / - p73 knockdown was performed to identify differentially expressed genes (DEGs). This was corroborated with three CRC tissue expression datasets available in Gene Expression Omnibus. Further analysis involved KEGG and Gene ontology to elucidate the functional roles of DEGs. The protein-protein interaction (PPI) network was constructed using Cytoscape to identify hub genes. Kaplan-Meier (KM) plots along with GEPIA and UALCAN database analysis provided the insights into the prognostic and diagnostic significance of these hub genes. Machine/deep learning algorithms were employed to perform TNM-stage classification. Transcriptome profiling revealed 1289 upregulated and 1897 downregulated genes. When intersected with employed CRC datasets, 284 DEGs were obtained. Comprehensive analysis using gene ontology and KEGG revealed enrichment of the DEGs in metabolic process, fatty acid biosynthesis, etc. The PPI network constructed using these 284 genes assisted in identifying 20 hub genes. Kaplan-Meier, GEPIA, and UALCAN analyses uncovered the clinicopathological relevance of these hub genes. Conclusively, the deep learning model achieved TNM-stage classification accuracy of 0.78 and 0.75 using 284 DEGs and 20 hub genes, respectively. The study represents a pioneer endeavor amalgamating transcriptomics, publicly available tissue datasets, and machine learning to unveil key CRC-associated genes. These genes are found relevant regarding the patients' prognosis and diagnosis. The unveiled biomarkers exhibit robustness in TNM-stage prediction, thereby laying the foundation for future clinical applications and therapeutic interventions in CRC management.
Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Protein Interaction Maps , Tumor Protein p73 , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Computational Biology/methods , Tumor Protein p73/genetics , Tumor Protein p73/metabolism , Protein Interaction Maps/genetics , Prognosis , HCT116 Cells , Transcriptome , Kaplan-Meier EstimateABSTRACT
BACKGROUND: Colorectal cancer (CRC) ranks third in cancer incidence globally and is the second leading cause of cancer-related mortality. The nucleoside diphosphate kinase 1 (NME1) and netrin 1 receptor (DCC) genes have been associated with resistance against tumorigenesis and tumor metastasis. This study investigates the potential association between NME1 (rs34214448 G > T and rs2302254 C > T) and DCC (rs2229080 G > C and rs714 A > G) variants and susceptibility to colorectal cancer development. METHODS: Samples from 232 colorectal cancer patients and 232 healthy blood donors underwent analysis. Variants were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were assessed using odds ratios (OR), and the p values were adjusted with Bonferroni test. RESULTS: Individuals carrying the G/T and T/T genotypes for the NME1 rs34214448 variant exhibited a higher susceptibility for develop colorectal cancer (OR = 2.68, 95% CI: 1.76-4.09, P = 0.001 and OR = 2.47, 95% CI: 1.37-4.47, P = 0.001, respectively). These genotypes showed significant associations in patients over 50 years (OR = 2.87, 95% CI: 1.81-4.54, P = 0.001 and OR = 2.99, 95% CI: 1.54-5.79, P = 0.001 respectively) and with early Tumor-Nodule-Metastasis (TNM) stage (P = 0.001), and tumor location in the rectum (P = 0.001). Furthermore, the DCC rs2229080 variant revealed that carriers of the G/C genotype had an increased risk for develop colorectal cancer (OR = 2.00, 95% CI: 1.28-3.11, P = 0.002) and were associated with age over 50 years, sex, and advanced TNM stages (P = 0.001). CONCLUSIONS: These findings suggest that the NME1 rs34214448 and DCC rs2229080 variants play a significant role in colorectal cancer development.
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Colorectal Neoplasms , Stomach Neoplasms , Humans , Middle Aged , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Genotype , Stomach Neoplasms/genetics , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Case-Control Studies , DCC Receptor/genetics , NM23 Nucleoside Diphosphate Kinases/geneticsABSTRACT
OBJECTIVE: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. METHODS: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. RESULTS: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. CONCLUSIONS: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal , Ki-67 Antigen , Neoplasm Grading , Pancreatic Neoplasms , Humans , Ki-67 Antigen/metabolism , Ki-67 Antigen/analysis , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/metabolism , Female , Male , Prognosis , Middle Aged , Aged , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/mortality , Retrospective Studies , Adult , Cell Differentiation , Neoplasm Staging , Biomarkers, Tumor/metabolism , Aged, 80 and over , PancreatectomyABSTRACT
BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death globally. LEM domain containing 1 (LEMD1) function has been identified in several cancers but not in NSCLC. OBJECTIVE: This study aimed to investigate the LEMD1 function in NSCLC. METHODS: NSCLC tissues were obtained from 66 patients, and LEMD1 expressions were measured using quantitative real-time PCR, immunohistochemical assay, and Western blot. Overall survival of NSCLC patients was estimated by the Kaplan-Meier method. Meanwhile, LEMD1 function and mechanism were assessed using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine analysis, Transwell, Sphere formation assay, and flow cytometry. Furthermore, LEMD1 function in vivo was evaluated by establishing a xenograft tumor model, hematoxylin-eosin staining, and immunohistochemical assay. RESULTS: LEMD1 was highly expressed in NSCLC tissues and was interrelated to tumor differentiation, TNM stage, and lymph node metastasis of patients. Overall survival of NSCLC patients with high LEMD1 was found to be lower than that of patients with low LEMD1. Functionally, interference with LEMD1 restrained NSCLC cell proliferation, invasion, and stemness characteristics. Mechanistically, LEMD1 facilitated the malignant phenotype of NSCLC, and 740 Y-P reversed this impact, prompting that LEMD1 aggravated NSCLC by activating PI3K/AKT pathway. Furthermore, LEMD1 knockdown hindered NSCLC proliferation in vivo. Conclusion: LEMD1 accelerated NSCLC cell proliferation, invasion, and stemness characteristics via activating PI3K/AKT pathway.
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Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/pathology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal TransductionABSTRACT
Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.
Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Extracellular Vesicles , Lung Neoplasms , Animals , Humans , Ligands , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Extracellular Vesicles/metabolism , B7-H1 Antigen , Fibrinogen/metabolismABSTRACT
BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.
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Endometrial Neoplasms , Female , Humans , United States , Australia/epidemiology , Registries , Neoplasm Staging , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/epidemiologyABSTRACT
OBJECTIVE: There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied. METHODS: A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the χ2 test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS). RESULTS: The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC. CONCLUSIONS: The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.
Subject(s)
Stomach Neoplasms , Humans , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/pathology , Prognosis , Gastrectomy , Lymphatic Metastasis , Fibrinogen , AlbuminsABSTRACT
(1) Background: Colorectal cancer is the third most common type of cancer with a high mortality rate and poor prognosis. The accurate prediction of key genetic mutations, such as the KRAS status, tumor staging, and extramural venous invasion (EMVI), is crucial for guiding personalized treatment decisions and improving patients' outcomes. MRI radiomics was assessed to predict the KRAS status and tumor staging in colorectal cancer patients across different imaging platforms to improve the personalized treatment decisions and outcomes. (2) Methods: Sixty colorectal cancer patients (35M/25F; avg. age 56.3 ± 12.9 years) were treated at an oncology unit. The MRI scans included T2-weighted (T2W) and diffusion-weighted imaging (DWI) or the apparent diffusion coefficient (ADC). The manual segmentation of colorectal cancer was conducted on the T2W and DWI/ADC images. The cohort was split into training and validation sets, and machine learning was used to build predictive models. (3) Results: The neural network (NN) model achieved 73% accuracy and an AUC of 0.71 during training for predicting the KRAS mutation status, while during testing, it achieved 62.5% accuracy and an AUC of 0.68. In the case of tumor grading, the support vector machine (SVM) model excelled with a training accuracy of 72.93% and an AUC of 0.7, and during testing, it reached an accuracy of 72% and an AUC of 0.69. (4) Conclusions: ML models using radiomics from ADC maps and T2-weighted images are effective for distinguishing KRAS genes, tumor grading, and EMVI in colorectal cancer. Standardized protocols are essential to improve MRI radiomics' reliability in clinical practice.
ABSTRACT
Background: Recent studies have shown that immune checkpoint inhibitors (ICIs) targeting programmed cell death-ligand 1 (PD-L1) have potential benefits in patients with non-small cell lung cancer (NSCLC) subgroups, while the clinicopathological characteristics associated with PD-L1 expression have not been well established. The purpose of this study was to detect the expression level of PD-L1 in tumor tissues of patients with advanced lung adenocarcinoma (ADC) and analyze its possible relationship with clinicopathological characteristics, so as to identify the predictors of PD-L1 expression. Methods: This retrospective study was conducted by analyzing the clinicopathological and imaging characteristics of hospitalized advanced lung ADC patients with PD-L1 available data and admitted to the respiratory department of our hospital. The expression level of PD-L1 in fresh-frozen tumor tissue samples of 136 advanced ADC patients was analyzed by immunohistochemistry. The patients were divided into positive and negative groups based on a cut-off of 1% PD-L1 expression level. Subsequently, the significant correlation between PD-L1 levels and clinicopathological features were evaluated. The predictive performance of clinicopathological characteristics on PD-L1 expression was evaluated and the optimal cut-off values were identified by plotting the receiver operating characteristic (ROC) curve. Results: The expression level of PD-L1 was related to sex, clinical stage, serum carcinoembryonic antigen (CEA), neuron specific enolase (NSE), white blood cell (WBC), and tumor (T) and metastasis (M) stage. Multivariate logistic regression analysis showed the CEA, NSE, T stage, and WBC were independent predictors of PD-L1 positive expression in lung ADC patients. The ROC curve suggested the model combining CEA with NSE [area under the curve (AUC) =0.815] could better predict the expression levels of PD-L1. The optimal cut-off values for identifying advanced lung ADC patients with PD-L1 positive were CEA ≤13.38 ng/mL and NSE ≤42.35 ng/mL, with sensitivity and specificity of 85.4% and 55.6%, and 92.7% and 32.1%, respectively. Conclusions: Some commonly used clinicopathological features are related to the histological expression of PD-L1. The serum CEA, NSE, T stage, and WBC values can be used as indicators to predict the expression level of PD-L1 in advanced lung ADC, and are used as predictors to evaluate the efficacy of ICIs before treatment.