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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone. Methods: In group 1, 236 IBD patients (145 Crohn's disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC). Results: Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52. Conclusion: In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Serum and glucocorticoid-induced protein kinase 1 (SGK1) is a member of the "AGC" subfamily of protein kinases, which shares structural and functional similarities with the AKT family of kinases and displays serine/threonine kinase activity. Aberrant expression of SGK1 has profound cellular consequences and is closely correlated with human cancer. SGK1 is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in the genesis and development of many human cancers. Abnormal expression of SGK1 has been found in tissue and may hopefully become a useful indicator of cancer progression. In addition, SGK1 acts as a prognostic factor for cancer patient survival. This review systematically summarizes and discusses the role of SGK1 as a diagnostic and prognostic biomarker of diverse cancer types; focuses on its essential roles and functions in tumorigenesis, cancer cell proliferation, apoptosis, invasion, metastasis, autophagy, metabolism, and therapy resistance and in the tumor microenvironment; and finally summarizes the current understanding of the regulatory mechanisms of SGK1 at the molecular level. Taken together, this evidence highlights the crucial role of SGK1 in tumorigenesis and cancer progression, revealing why it has emerged as a potential target for cancer therapy. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.