Search

Abstract Background The tachykinin receptor 2 (TACR2) is encoded by the tachykinin receptor correlation gene. Recent microarray analysis for prostate cancer suggests that TACR2 expression is associated with clinical phenotype and disease-free survival among patients with prostate cancer. Results TACR2 protein levels were lower in prostate cancer tissues than in adjacent normal prostate tissue. TACR2 expression significantly correlated with clinical stage, Gleason scores, and survival outcomes. TACR2 expression positively correlated with mast cells and negatively correlated with M2 macrophages. Overexpression of TACR2 promoted the migration and proliferation of prostate cancer cells by regulating the Wnt signaling pathway. Conclusions The TACR2-Wnt/β-catenin signaling pathway is critical in prostate cancer. TACR2 may affect tumor cells’ occurrence and development by changing the content of immune cells in the tumor microenvironment. These findings suggest that TACR2 may be a candidate molecular biomarker for prostate cancer therapy.

Background and purpose: Inhibitors of poly (ADP-ribose) polymerase (PARPi) has been shown in multiple clinical trials to benefit survival in patients with homologous recombination repair (HRR) gene mutations in metastatic castration-resistant prostate cancer (mCRPC). Fluzoparib has been approved for the treatment of ovarian, fallopian tube and peritoneal cancers, but no data have been reported for prostate cancer. The purpose of this study was to evaluate the efficacy and safety of fluzoparib in the treatment of patients with prostate cancer. Methods: The clinical data of 13 mCRPC patients treated with fluzoparib alone or fluzoparib combined with abiraterone or SHR3680 (androgen receptor antagonist) in 9 hospitals nationwide including Fudan University Shanghai Cancer Center from January 1, 2020 to February 1, 2021 were retrospectively analyzed. Genetic mutation data, survival data, adverse reactions and other data were obtained through outpatient cases or telephone follow-up. Results: Among the 13 patients, 3 patients were treated with fluzoparib alone, 8 patients were treated with fluzoparib combined with abiraterone, and 2 patients were treated with fluzoparib combined with SHR3680. All the 3 patients treated with monotherapy carried HRR gene mutations, and all had prostate-specific antigen (PSA); among those, 2 patients (66.7%) had PSA decrease of more than 50%. All the 8 patients treated with fluzoparib combined with abiraterone had been resistant to abiraterone at the earlier stage, and the genetic testing results showed that 2 patients did not carry HRR pathogenic mutation, and 1 patient did not receive genetic testing. Among the 8 patients, only 1 patient without HRR pathogenic mutation had an increase in PSA after receiving the combined treatment, while the remaining 7 patients (87.5%) had a decrease in PSA. PSA decreased by more than 50% in 3 patients (37.5%) and 90% in 2 patients (25.0%). The 2 patients treated with fluzoparib combined with SHR3680 had been resistant to abiraterone and docetaxel at the earlier stage, one patient had no genetic test and no PSA response, and the other patient had no DNA damage repair (DDR) gene mutation, however, decreased by more than 50%. At the same time, 61.5% (8/13) of the patients showed different degrees of adverse reactions, the main adverse reactions were anemia, joint pain, loss of appetite and fatigue; 23.1% (3/13) of the patients developed grade 3 anemia, of whom 1 patient terminated the treatment. Conclusion: Fluzoparib shows promising clinical prospects, and is well tolerated in both monotherapy and combination therapy. However, this conclusion needs to be further confirmed in prospective clinical studies with larger sample size.

Indolethylamine-N-methyltransferase (INMT) is a methyltransferase downregulated in lung cancer, meningioma, and prostate cancer; however, its role and mechanism in prostate cancer remain unclear. By analyzing The Cancer Genome Atlas (TCGA)-PRAD, we found that the expression of INMT in prostate cancer was lower than that of adjacent non-cancerous prostate tissues and was significantly correlated with lymph node metastasis Gleason score, PSA expression, and survival. Combined with the GSE46602 cohorts for pathway enrichment analysis, we found that INMT was involved in regulating the MAPK, TGFβ, and Wnt signaling pathways. After overexpression of INMT in prostate cancer cell lines 22Rv1 and PC-3, we found an effect of INMT on these tumor signal pathways; overexpression of INMT inhibited the proliferation of prostate cancer cells and promoted apoptosis. Using the ESTIMATE algorithm, we found that with the increase of INMT expression, immune and stromal scores in the tumor microenvironment increased, immune response intensity increased, and tumor purity decreased. The difference in INMT expression affected the proportion of several immune cells. According to PRISM and CTRP2.0, the potential therapeutic agents associated with the INMT expression subgroup in TCGA were predicted. The area under the curve (AUC) values of 26 compounds positively correlated with the expression of INMT, while the AUC values of 14 compounds were negatively correlated with the expression of INMT. These findings suggest that INMT may affect prostate cancer’s occurrence, development, and drug sensitivity via various tumor signaling pathways and tumor microenvironments.