Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2023 ASH annual meeting.

Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based therapies specifically tailored for those with R/R AML remains scarce. Here, we provide a comprehensive overview of the latest data presented at the 65th American Society of Hematology Annual Meeting, shedding light on the progress and efficacy of VEN-based therapies for R/R AML.

Emerging proteins involved in castration­resistant prostate cancer via the AR­dependent and AR­independent pathways (Review).

Despite achieving optimal initial responses to androgen deprivation therapy, most patients with prostate cancer eventually progress to a poor prognosis state known as castration­resistant prostate cancer (CRPC). Currently, there is a notable absence of reliable early warning biomarkers and effective treatment strategies for these patients. Although androgen receptor (AR)­independent pathways have been discovered and acknowledged in recent years, the AR signaling pathway continues to play a pivotal role in the progression of CRPC. The present review focuses on newly identified proteins within human CRPC tissues. These proteins encompass both those involved in AR­dependent and AR­independent pathways. Specifically, the present review provides an in­depth summary and analysis of the emerging proteins within AR bypass pathways. Furthermore, the significance of these proteins as potential biomarkers and therapeutic targets for treating CRPC is discussed. Therefore, the present review offers valuable theoretical insights and clinical perspectives to comprehensively enhance the understanding of CRPC.

Exosomal miR-222-3p contributes to castration-resistant prostate cancer by activating mTOR signaling.

Despite the clinical benefits of androgen deprivation therapy, most patients with advanced androgen-dependent prostate cancer (ADPC) eventually relapse and progress to lethal androgen-independent prostate cancer (AIPC), also termed castration-resistant prostate cancer (CRPC). MiRNAs can be packaged into exosomes (Exos) and shuttled between cells. However, the roles and mechanisms of exosomal miRNAs involved in CRPC progression have not yet been fully elucidated. Here, we find that miR-222-3p is elevated in AIPC cells, which results in remarkable enhancement of cell proliferation, migration, and invasion ability. Furthermore, Exos released by AIPC cells can be uptaken by ADPC cells, thus acclimating ADPC cells to progressing to more aggressive cell types in vitro and in vivo through exosomal transfer of miR-222-3p. Mechanistically, Exos-miR-222-3p promoted ADPC cells transformed to AIPC-like cells, at least in part, by activating mTOR signaling through targeting MIDN. Our results show that AIPC cells secrete Exos containing miRNA cargo. These cargos can be transferred to ADPC cells through paracrine mechanisms that have a strong impact on cellular functional remodeling. The current work underscores the great therapeutic potential of targeting Exo miRNAs, either as a single agent or combined with androgen receptor pathway inhibitors for CRPC treatment.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting.

Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

New insights into lipid metabolism and prostate cancer (Review).

Prostate cancer (PCa) is the most common malignant tumor of the male urological system and poses a severe threat to the survival of middle­aged and elderly males worldwide. The development and progression of PCa are affected by a variety of biological processes, including proliferation, apoptosis, migration, invasion and the maintenance of membrane homeostasis of PCa cells. The present review summarizes recent research advances in lipid (fatty acid, cholesterol and phospholipid) metabolic pathways in PCa. In the first section, the metabolism of fatty acids is highlighted, from formation to catabolism and associated proteins. Subsequently, the role of cholesterol in the pathogenesis and evolution of PCa is described in detail. Finally, the different types of phospholipids and their association with PCa progression is also discussed. In addition to the impact of key proteins of lipid metabolism on PCa growth, metastasis and drug resistance, the present review also summarizes the clinical value of fatty acids, cholesterol and phospholipids, as diagnostic and prognostic indicators and therapeutic targets in PCa.

Adefovir dipivoxil inhibits APL progression through degradation of the oncoprotein PML-RARA.

Acute promyelocytic leukemia (APL) is highly aggressive and is frequently associated with disseminated intravascular coagulation and high early death rates. Although all-trans retinoic acid (RA) induces complete remission in a high proportion of patients with APL, there are limited treatments for APL patients with RA resistance. Here we report an atypical APL patient, with an APL-like disease that developed very slowly without anti-leukemia therapy for nearly 2 years. During that time, the patient only intermittently received anti-HBV drugs, i.e., the combination of adefovir dipivoxil (ADV) and entecavir (ETV), leading us to hypothesize that ADV and/or ETV could inhibit APL progression. Our results showed that anti-HBV drugs ADV and ETV both exhibited significantly inhibitory effects on APL cells, and ADV indicated a much greater cytotoxic effect than ETV on APL cells. We further found that ADV significantly promoted APL cell differentiation and apoptosis, thereby restraining the progression of APL. Most importantly, our study uncovered a novel mechanism of ADV prohibiting APL progression, which was mediated, at least in part, by inhibition of TRIB3 and degradation of the oncoprotein PML-RARA, therefore leading to APL cell differentiation and apoptosis. Taken together, our study demonstrated that ADV, an anti-HBV drug, had significantly inhibitory effects on APL, and provided a novel therapeutic strategy for APL patients with RA resistance.

[Corrigendum] RON and c­Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells.

Subsequently to the publication of the above article, the authors have discovered that the version of Fig. 5 included in the paper was an incorrect version, and that two pairs of data panels were inadvertently included in Fig. 6D (the data panels for the NC+migration and NC+HGF+U0126+invasion experiments for the PC3 cells, and the data panels for the NC+invasion and NC+HGF+U0126+invasion experiments for the DU145 cells) that contained overlapping data derived from the same source. These data were intended to represent the results obtained under different experimental conditions. Furthermore, the GAPDH control bands in Fig. 4A (DU145 cells) and the p­ERK1/2 bands in Fig. 6A (PC3 cells) were incorrectly chosen for these figures. After having consulted the original data, the authors discovered that unintended errors were made in assembling the data for these graphs. In uploading the corrected version of Fig. 5, Fig. 3C and D and Fig. 4C and D were adjusted accordingly. The corrected versions of Figs. 3, 4, 5, and 6 are shown on the subsequent pages. The authors regret the errors that were made during the preparation of the published figures, and confirm that these errors did not affect the conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 37: 3209­3218, 2017; DOI: 10.3892/or.2017.5585].

Identification and Validation of Three Hub Genes Involved in Cell Proliferation and Prognosis of Castration-Resistant Prostate Cancer.

Background: The acquisition of castration resistance is lethal and inevitable in most prostate cancer patients under hormone therapy. However, effective biomarkers and therapeutic targets for castration-resistant prostate cancer remain to be defined. Methods: Comprehensive bioinformatics tools were used to screen hub genes in castration-resistant prostate cancer and were verified in androgen-dependent prostate cancer and castration-resistant prostate cancer in TCGA and the SU2C/PCF Dream Team database, respectively. Gene set enrichment analysis and in vitro experiments were performed to determine the potential functions of hub genes involved in castration-resistant prostate cancer progression. Results: Three hub genes were screened out by bioinformatics analysis: MCM4, CENPI, and KNTC1. These hub genes were upregulated in castration-resistant prostate cancer and showed high diagnostic and prognostic value. Moreover, the expression levels of the hub genes were positively correlated with neuroendocrine prostate cancer scores, which represent the degree of castration-resistant prostate cancer aggression. Meanwhile, in vitro experiments confirmed that hub gene expression was increased in castration-resistant prostate cancer cell lines and that inhibition of hub genes hindered cell cycle transition, resulting in suppression of castration-resistant prostate cancer cell proliferation, which confirmed the gene set enrichment analysis results. Conclusions: MCM4, CENPI, and KNTC1 could serve as candidate diagnostic and prognostic biomarkers of castration-resistant prostate cancer and may provide potential preventive and therapeutic targets.

Emerging Proteins in CRPC: Functional Roles and Clinical Implications.

Prostate cancer (PCa) is the most common cancer in men in the western world, but the lack of specific and sensitive markers often leads to overtreatment of prostate cancer which eventually develops into castration-resistant prostate cancer (CRPC). Novel protein markers for diagnosis and management of CRPC will be promising. In this review, we systematically summarize and discuss the expression pattern of emerging proteins in tissue, cell lines, and serum when castration-sensitive prostate cancer (CSPC) progresses to CRPC; focus on the proteins involved in CRPC growth, invasion, metastasis, metabolism, and immune microenvironment; summarize the current understanding of the regulatory mechanisms of emerging proteins in CSPC progressed to CRPC at the molecular level; and finally summarize the clinical applications of emerging proteins as diagnostic marker, prognostic marker, predictive marker, and therapeutic marker.

Encapsulation Efficiency and Functional Stability of Cinnamon Essential Oil in Modified ß-cyclodextrins: In Vitro and In Silico Evidence.

Essential oils (EOs) have good natural antioxidant and antimicrobial properties; however, their volatility, intense aroma, poor aqueous solubility, and chemical instability limit their applications in the food industry. The encapsulation of EOs in ß-cyclodextrins (ß-CDs) is a widely accepted strategy for enhancing EO applications. The complexation of cinnamon essential oil (CEO) with five types of ß-CDs, containing different substituent groups (ß-CD with primary hydroxyl, Mal-ß-CD with maltosyl, CM-ß-CD with carboxymethyl, HP-ß-CD with hydroxypropyl, and DM-ß-CD with methyl), inclusion process behaviors, volatile components, and antioxidant and antibacterial activities of the solid complexes were studied. The CEOs complexed with Mal-ß-CD, CM-ß-CD, and ß-CD were less soluble than those complexed with DM-ß-CD and HP-ß-CD. Molecular docking confirmed the insertion of the cinnamaldehyde benzene ring into various ß-CD cavities via hydrophobic interactions and hydrogen bonds. GC-MS analysis revealed that HP-ß-CD had the greatest adaptability to cinnamaldehyde. The CEO encapsulated in ß-, Mal-ß-, and CM-ß-CD showed lower solubility but better control-release characteristics than those encapsulated in DM- and HP-ß-CD, thereby increasing their antioxidant and antibacterial activities. This study demonstrated that ß-, Mal-ß-, and CM-ß-CD were suitable alternatives for the encapsulation of CEO to preserve its antioxidant and antibacterial activities for long-time use.

A Multivariate Diagnostic Model Based on Urinary EpCAM-CD9-Positive Extracellular Vesicles for Prostate Cancer Diagnosis.

INTRODUCTION: Prostate cancer (PCa) is one of the most frequently diagnosed cancers and the leading cause of cancer death in males worldwide. Although prostate-specific antigen (PSA) screening has considerably improved the detection of PCa, it has also led to a dramatic increase in overdiagnosing indolent disease due to its low specificity. This study aimed to develop and validate a multivariate diagnostic model based on the urinary epithelial cell adhesion molecule (EpCAM)-CD9-positive extracellular vesicles (EVs) (uEVEpCAM-CD9) to improve the diagnosis of PCa. METHODS: We investigated the performance of uEVEpCAM-CD9 from urine samples of 193 participants (112 PCa patients, 55 benign prostatic hyperplasia patients, and 26 healthy donors) to diagnose PCa using our laboratory-developed chemiluminescent immunoassay. We applied machine learning to training sets and subsequently evaluated the multivariate diagnostic model based on uEVEpCAM-CD9 in validation sets. RESULTS: Results showed that uEVEpCAM-CD9 was able to distinguish PCa from controls, and a significant decrease of uEVEpCAM-CD9 was observed after prostatectomy. We further used a training set (N = 116) and constructed an exclusive multivariate diagnostic model based on uEVEpCAM-CD9, PSA, and other clinical parameters, which showed an enhanced diagnostic sensitivity and specificity and performed excellently to diagnose PCa [area under the curve (AUC) = 0.952, P < 0.0001]. When applied to a validation test (N = 77), the model achieved an AUC of 0.947 (P < 0.0001). Moreover, this diagnostic model also exhibited a superior diagnostic performance (AUC = 0.917, P < 0.0001) over PSA (AUC = 0.712, P = 0.0018) at the PSA gray zone. CONCLUSIONS: The multivariate model based on uEVEpCAM-CD9 achieved a notable diagnostic performance to diagnose PCa. In the future, this model may potentially be used to better select patients for prostate transrectal ultrasound (TRUS) biopsy.

Glycolysis-related gene expression profiling serves as a novel prognosis risk predictor for human hepatocellular carcinoma.

Metabolic pattern reconstruction is an important factor in tumor progression. Metabolism of tumor cells is characterized by abnormal increase in anaerobic glycolysis, regardless of high oxygen concentration, resulting in a significant accumulation of energy from glucose sources. These changes promotes rapid cell proliferation and tumor growth, which is further referenced a process known as the Warburg effect. The current study reconstructed the metabolic pattern in progression of cancer to identify genetic changes specific in cancer cells. A total of 12 common types of solid tumors were included in the current study. Gene set enrichment analysis (GSEA) was performed to analyze 9 glycolysis-related gene sets, which are implicated in the glycolysis process. Univariate and multivariate analyses were used to identify independent prognostic variables for construction of a nomogram based on clinicopathological characteristics and a glycolysis-related gene prognostic index (GRGPI). The prognostic model based on glycolysis genes showed high area under the curve (AUC) in LIHC (Liver hepatocellular carcinoma). The findings of the current study showed that 8 genes (AURKA, CDK1, CENPA, DEPDC1, HMMR, KIF20A, PFKFB4, STMN1) were correlated with overall survival (OS) and recurrence-free survival (RFS). Further analysis showed that the prediction model accurately distinguished between high- and low-risk cancer patients among patients in different clusters in LIHC. A nomogram with a well-fitted calibration curve based on gene expression profiles and clinical characteristics showed good discrimination based on internal and external cohorts. These findings indicate that changes in expression level of metabolic genes implicated in glycolysis can contribute to reconstruction of tumor-related microenvironment.

Five-gene signature associating with Gleason score serve as novel biomarkers for identifying early recurring events and contributing to early diagnosis for Prostate Adenocarcinoma.

Background: Compared to non-recurrent type, recurrent prostate adenocarcinoma (PCa) is highly fatal, and significantly shortens the survival time of affected patients. Early and accurate laboratory diagnosis is particularly important in identifying patients at high risk of recurrence, necessary for additional systemic intervention. We aimed to develop efficient and accurate diagnostic and prognostic biomarkers for new PCa following radical therapy. Methods: We identified differentially expressed genes (DEGs) and clinicopathological data of PCa patients from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) repositories. We then uncovered the most relevant clinical traits and genes modules associated with PCa prognosis using the Weighted gene correlation network analysis (WGCNA). Univariate Cox regression analysis and multivariate Cox proportional hazards (Cox-PH) models were performed to identify candidate gene signatures related to Disease-Free Interval (DFI). Data for internal and external cohorts were utilized to test and validate the accuracy and clinical utility of the prognostic models. Results: We constructed and validated an accurate and reliable model for predicting the prognosis of PCa using 5 Gleason score-associated gene signatures (ZNF695, CENPA, TROAP, BIRC5 and KIF20A). The ROC and Kaplan-Meier analysis revealed the model was highly accurate in diagnosing and predicting the recurrence and metastases of PCa. The accuracy of the model was validated using the calibration curves based on internal TCGA cohort and external GEO cohort. Using the model, patients could be prognostically stratified in to various groups including TNM classification and Gleason score. Multivariate analysis revealed the model could independently predict the prognosis of PCa patients and its utility was superior to that of clinicopathological characteristics. In addition, we fund the expression of the 5 gene signatures strongly and positively correlated with tumor purity but negatively correlated with infiltration CD8+ T cells to the tumor microenvironment. Conclusions: A 5 gene signatures can accurately be used in the diagnosis and prediction of PCa prognosis. Thus this can guide the treatment and management prostate adenocarcinoma.

The MYH9 Cytoskeletal Protein Is a Novel Corepressor of Androgen Receptors.

In the progression of castration-resistant prostate cancer (CRPC), the androgen receptor (AR) that serves as a transcription factor becomes the most remarkable molecule. The transcriptional activity of AR is regulated by various coregulators. As a result, altered expression levels, an aberrant location or activities of coregulators promote the development of prostate cancer. We describe herein results showing that compared with androgen-dependent prostate cancer (ADPC) cells, AR nuclear translocation capability is enhanced in androgen-independent prostate cancer (AIPC) cells. To gain insight into whether AR coregulators are responsible for AR translocation capability, we performed coimmunoprecipitation (CO-IP) coupled with LC-MS/MS to screen 27 previously reported AR cofactors and 46 candidate AR cofactors. Furthermore, one candidate, myosin heavy chain 9 (MYH9), was identified and verified as a novel AR cofactor. Interestingly, the distribution of MYH9 was in both the cytoplasmic and nuclear compartments yet was enriched in the nucleus when AR was knocked down by AR shRNA, suggesting that the nuclear translocation of MYH9 was negatively regulated by AR. In addition, we found that blebbistatin, an inhibitor of MYH9, not only promoted AR nuclear translocation but also enhanced the expression of the AR target gene PSA, which indicates that MYH9 represses nuclear AR signaling. Taken together, our findings reveal that MYH9 appears to be a novel corepressor of AR plays a pivotal role in the progression of CRPC.

Computed tomography image fusion, Coaxial guidewire technique, Fast intraprocedural cortisol testing technique improves success rate and decreases radiation exposure, procedure time, and contrast use for adrenal vein sampling.

BACKGROUND: Adrenal vein sampling (AVS) is recommended for discriminating patients with unilateral primary aldosteronism from bilateral disease. However, it is a technically demanding procedure that is markedly underused. We developed a computed tomography image fusion, coaxial guidewire technique, fast intraprocedural cortisol testing (CCF) technique to improve AVS success rate, which combines CT image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing. OBJECTIVE: To evaluate the effectiveness and safety of the AVS--CCF technique. METHODS: We retrospectively evaluated 105 patients who undervent AVS from June 2016 to October 2020. There were 51 patients in the AVS--CCF group and 54 patients in the AVS group. We compared two groups with technical success rate, procedure time, radiation exposure, volume of contrast medium, and complications (adrenal vein rupture, dissection, infarction, or thrombosis; intraglandular or periadrenal hematoma; and contrast-induced nephropathy). RESULTS: The technical success rate was higher for AVS--CCF than for AVS without CCF (98 vs. 83.3% for bilateral adrenal veins, P = 0.016). AVS--CCF was associated with a shorter procedure time (63.6 ±â€Š24.6 vs. 94.8 ±â€Š40.8 min, P < 0.001), shorter fluoroscopy time (15.6 ±â€Š12.6 vs. 20.4 ±â€Š15.0 min, P = 0.043), and lower contrast medium volume (25.10 ±â€Š21.82 vs. 44.1 ±â€Š31.0 ml, P < 0.001). There were no significant differences between groups with respect to the time for cannulating the left or right adrenal vein or the peak skin radiation dose. Adrenal vein rupture occurred in 14 patients and intraglandular hematoma in 1 patient. CONCLUSION: The CCF technique during AVS not only contributed to improved technical success rates but also associated with decreased procedure time, radiation exposure, and contrast medium volume.

Emerging roles and mechanisms of microRNA­222­3p in human cancer (Review).

MicroRNAs (miRNAs/miRs) are a class of small non­coding RNAs that maintain the precise balance of various physiological processes through regulating the function of target mRNAs. Dysregulation of miRNAs is closely associated with various types of human cancer. miR­222­3p is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in tumor occurrence and progression. miR­222­3p in human biofluids, such as urine and plasma, may be a potential biomarker for the early diagnosis of tumors. In addition, miR­222­3p acts as a prognostic factor for the survival of patients with cancer. The present review first summarizes and discusses the role of miR­222­3p as a biomarker for diverse types of cancers, and then focuses on its essential roles in tumorigenesis, progression, metastasis and chemoresistance. Finally, the current understanding of the regulatory mechanisms of miR­222­3p at the molecular level are summarized. Overall, the current evidence highlights the crucial role of miR­222­3p in cancer diagnosis, prognosis and treatment.

Integrated Analysis to Obtain Potential Prognostic Signature in Glioblastoma.

Glioblastoma multiforme (GBM) is the most malignant and multiple tumors of the central nervous system. The survival rate for GBM patients is less than 15 months. We aimed to uncover the potential mechanism of GBM in tumor microenvironment and provide several candidate biomarkers for GBM prognosis. In this study, ESTIMATE analysis was used to divide the GBM patients into high and low immune or stromal score groups. Microenvironment associated genes were filtered through differential analysis. Weighted gene co-expression network analysis (WGCNA) was performed to correlate the genes and clinical traits. The candidate genes' functions were annotated by enrichment analyses. The potential prognostic biomarkers were assessed by survival analysis. We obtained 81 immune associated differentially expressed genes (DEGs) for subsequent WGCNA analysis. Ten out of these DEGs were significantly associated with targeted molecular therapy of GBM patients. Three genes (S100A4, FCGR2B, and BIRC3) out of these genes were associated with overall survival and the independent test set testified the result. Here, we obtained three crucial genes that had good prognostic efficacy of GBM and may help to improve the prognostic prediction of GBM.

Prostatic aspirated cellular RNA analysis enables fast diagnosis and staging of prostate cancer.

OBJECTIVE: The aim of this study is to investigate the potential application of prostatic aspirated cellular RNA analysis technique for fast diagnosing and staging prostate cancer. METHODS: Prostatic aspirated cells were obtained immediately after transrectal ultrasound (TRUS)-guided needle biopsy. Cellular RNA such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, prostate specific antigen (PSA) mRNA and prostate-specific RNA (PCA3) mRNA were analyzed by using Reverse Transcription-Polymerase Chain Reaction (RT-PCR). PCA3 score was calculated as the ratio of PCA3 mRNA to PSA mRNA expression. Diagnostic performance of the fast-aspirated cellular RNA analysis technique for determining prostate cancer and metastatic status were evaluated by developing receiver operating characteristic curves (ROC), and the correlation between aspirated cellular RNA mRNA expressions and risk grouping was calculated, to investigate the underlying potential for PCa staging. RESULTS: PCA3 score was significantly higher in prostatic aspirated cells obtained from cancerous tissues than noncancerous tissues. The median aspirated cellular PCA3 score was higher in patients with PCa compared to BPH, and presenting an area under the ROC curve (AUC) of 0.87 (95%CI: 0.79-0.94) for PCa diagnosis. Multivariate regression analysis revealed that baseline median aspirated cellular PCA3 score (OR=9.316, 95%CI: 1.045-83.033, P<0.05) was an independent predictive factor for metastatic status in PCa patients. CONCLUSION: The ease of use and minimal complexity of fast prostatic aspirated cellular RNA analysis may be a valuable diagnostic technique, providing urgent diagnostic information for accurate PCa diagnosing and staging.

Integrated profiling identifies SLC5A6 and MFAP2 as novel diagnostic and prognostic biomarkers in gastric cancer patients.

Gastric cancer (GC) is one of the leading causes of malignancy­associated mortality worldwide. However, the underlying molecular mechanisms of GC are unclear and the prognosis of GC is poor. Therefore, it is important and urgent to explore the underlying mechanisms and screen for novel diagnostic and prognostic biomarkers, as well as therapeutic targets. In the current study, scale­free gene co­expression networks were constructed using weighted gene co­expression network analysis, the potential associations between gene sets and clinical features were investigated, and the hub genes were identified. The gene expression profiles of GSE38749 were downloaded from the Gene Expression Omnibus database. RNA­seq and clinical data for GC from The Cancer Genome Atlas were utilized for verification. Furthermore, the expression of candidate biomarkers in gastric tissues was investigated. Survival analysis was performed using Kaplan­Meier and log­rank test. The predictive role of candidate biomarkers in GC was evaluated using a receiver operator characteristic (ROC) curve. Gene Ontology, gene set enrichment analysis and gene set variation analysis methods were used to interpret the function of candidate biomarkers in GC. A total of 29 modules were identified via the average linkage hierarchical clustering. A significant module consisting of 48 genes associated with clinical traits was found; three genes with high connectivity in the clinical significant module were identified as hub genes. Among them, SLC5A6 and microfibril­associated protein 2 (MFAP2) were negatively associated with the overall survival, and their expression was elevated in GC compared with non­tumor tissues. Additionally, ROC curves indicated that SLC5A6 and MFAP2 showed a good diagnostic power in discriminating cancerous from normal tissues. SLC5A6 and MFAP2 were identified as novel diagnostic and prognostic biomarkers in GC patients; both of these genes were first reported here in connection with GC and deserved further research.