LncRNA NEAT1-associated aerobic glycolysis blunts tumor immunosurveillance by T cells in prostate cancer.

Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is nuclear-located and transcribed from chromatin 11. To date, little is known about the cellular functions and regulatory mechanisms of NEAT1 in prostate cancer (PCa). In this study, whole-genome RNA sequencing data were downloaded from TCGA and GEO databases. Biological information was used to analyze the different expressions of NEAT1. In situ hybridization (ISH) was performed to detect the expression of NEAT1 in PCa and paracarcinoma clinical samples. Then, NEAT1 was knocked down in PC3 cells through lentiviral infection with a plasmid construct. Bioinformatics and integrative analytical approaches were utilized to identify the relationships of NEAT1 with specific cancer-related gene sets. Cell proliferation assay and colony formation assay were performed to evaluate the cell proliferative ability. Glycolysis stress test, metabolism assay, and infiltrating T-cell function analysis were implemented to assess the changes in metabolism and immune microenvironment of PCa. We found that the expression of NEAT1 was higher in PCa than in non-neoplastic tissues. The cell proliferative capability of PCa cells was significantly reduced in the NEAT1 knockdown group. PCR array and bioinformatics analysis revealed that the enrichment of acidic substance-related gene sets was associated with NEAT1 expression. NEAT1 depletion inhibited PCa cell aerobic glycolysis accompanied by the reduction of lactate levels in the medium. Further, we found that lactate dehydrogenase A (LDHA) expression was positively regulated by NEAT1. At last, co-culture systems indicated that NEAT1 or LDHA knockdown promoted the secretion of CD8+ T-lymphocyte factors, including TNF-α, IFN-γ, and Granzyme B, and enhanced the antitumor effects.

[Relationship of prostate volume and inflammatory cell infiltration with the positive rate of prostate biopsy].

OBJECTIVE: To investigate the factors influencing the positive rate of prostate biopsy and its relationship with the prostate volume and inflammatory cell infiltration (ICI). METHODS: We retrospectively analyzed the clinical data on 230 cases of double-plane transrectal ultrasound-guided prostate biopsy in our Department of Urology, including the patients' age, body mass index (BMI), serum total prostate-specific antigen (tPSA), PSA density (PSAD), prostate volume, and ICI in the prostate tissue. We also investigated the relationship of the above factors with the pathological results of prostate biopsy by binary logistic regression analysis. RESULTS: The positive rate of prostate biopsy was 38.7% (89/230) in the total number of cases, 28.57% (n = 56) in the 196 cases with tPSA < 100 µg/L, and 97.06% (n = 33) in the 34 cases with tPSA ≥ 100 µg/L. Binary logistic regression analysis showed that the positive rate of prostate biopsy in those with tPSA < 100 µg/L was correlated positively with age (P < 0.01, OR = 1.09), tPSA (P < 0.01, OR = 1.04) and PSAD (P < 0.01, OR = 10.04), negatively with the prostate volume (P < 0.01, OR = 0.98) and ICI (P < 0.01, OR = 0.22), but not with BMI (P > 0.05). As a predictor of positive prostate biopsy, tPSA > 10 µg/L exhibited a sensitivity of 82.14% and a specificity of 35.71%, while PSAD > 0.26 showed a sensitivity of 78.57% and a specificity of 71.43%. CONCLUSIONS: Non-specific elevation of the tPSA level induced by increased prostate volume and inflammatory cell infiltration may lead to unnecessary biopsies in some patients. As a predictor of positive prostate biopsy, PSAD > 0.26 has a higher clinical application value than tPSA > 10 µg/L.