We have previously demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we revealed the mechanism of gut microbiota-derived short-chain fatty acids (SCFAs) as a mediator linking CRPC microbiota dysbiosis and prostate cancer (PCa) progression. By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell and macrophage recruitment assays, we examined the effects of CRPC fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Our results showed that FMT with CRPC patients' fecal suspension increased SCFAs-producing gut microbiotas such as Ruminococcus, Alistipes, Phascolarctobaterium in TRAMP mice, and correspondingly raised their gut SCFAs (acetate and butyrate) levels. CRPC FMT or SCFAs supplementation significantly accelerated mice's PCa progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Meanwhile, autophagy of PCa cells released higher level of chemokine CCL20 that could reprogramme the tumor microenvironment by recruiting more macrophage infiltration and simultaneously polarizing them into M2 type, which in turn further strengthened PCa cells invasiveness. Finally in a cohort of 362 PCa patients, we demonstrated that CCL20 expression in prostate tissue was positively correlated with Gleason grade, pre-operative PSA, neural/seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Collectively, CRPC gut microbiota-derived SCFAs promoted PCa progression via inducing cancer cell autophagy and M2 macrophage polarization. CCL20 could become a biomarker for prediction of prognosis in PCa patients. Intervention of SCFAs-producing microbiotas may be a useful strategy in manipulation of CRPC.

Renal mass biopsy using Raman spectroscopy identifies malignant and benign renal tumors: potential for pre-operative diagnosis

Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist’s experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928–0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953–1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.