Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer.

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.

[A multi-omics study on NKX3.1-related node genes in prostate cancer].

Objective: The NKX3.1 homeobox gene is closely associated with the development and progression of prostate cancer. This study was to explore NKX3.1-related down-stream node genes and their possible regulating mechanisms in prostate cancer. Methods: By multi-omics analysis of the TCGA data on prostate cancer,we screened 5 node genes in the down-stream signaling pathways that were possibly related to NKX3.1.We achieved the overexpression of NKX3.1 in prostate cancer by transfecting the prostate cancer PC-3 cell lines with the NKX3.1 expression vector and determined the expression levels of the node genes by real-time PCR. Results: Based on the results of multi-omics analysis,MAZ,LPAR3,TUBB2A,CAMKK2 and CPT1B were identified as the node genes involved in the NKX3.1-related signaling pathways in prostate cancer. The NKX3.1 overexpression experiments showed that the CAMKK2 and CPT1B genes were up-regulated 3. 439 and 4. 641 times respectively and the MAZ gene down-regulated 5.236 times in the prostate cancer PC-3 cells with the overexpression of NKX3.1. Conclusion: NKX3.1 may suppress the development and progression of prostate cancer by down-regulating the expression of MAZ and up-regulating those of CAMKK2 and CPT1B,and it may also be involved in the regulation of the metabolic process of prostate cancer through the CAMKK2 down-stream signaling pathway and CPT1B.

[Reduced zinc concentration in expressed prostatic secretion relates to the pain symptoms of types â ¢ and â £ prostatitis].

OBJECTIVE: To determine the zinc levels in the expressed prostatic secretion (EPS) of the patients with different types of chronic nonbacterial prostatitis, and explore the reference value of zinc concentration in EPS in the diagnosis and treatment of prostatitis. METHODS: We collected EPS samples from 35 healthy men and 173 patients with chronic nonbacterial prostatitis, including 65 cases of type ⅢA, 69 cases of type ⅢB, and 39 cases of type Ⅳ, according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We compared the zinc levels in the EPS samples among different groups and analyzed the correlations of zinc concentration with the NIH-CPSI scores, WBC count, pH value, and age of the subjects. RESULTS: The participants were aged 17－65 (32.5±8.5) years. The zinc concentrations in the EPS were significantly lower in the ⅢA (ï¼»162.2±10.8ï¼½ µg/ml) and ⅢB (ï¼»171.2±12.0ï¼½ µg/ml) than in the Ⅳ (ï¼»234.6±17.9ï¼½ µg/ml) (P<0.05 ) and the control group (ï¼»259.5±14.6ï¼½ µg/ml) (P<0.05 ). The zinc level was correlated negatively with the NIH-CPSI pain score (r=－0.248, P<0.01), quality of life score (r=－0.232, P<0.01), severity score (r=－0.270, P<0.01), total NIH-CPSI score (r=－0.281, P<0.01), and the pH value in EPS (r=－0.208, P<0.01), but showed no correlation with the WBC count and age of the subjects. CONCLUSIONS: The reduced zinc concentration in the EPS of the patients with chronic nonbacterial prostatitis may be associated with the pain symptoms of the disease, which suggests the potential reference value of measuring the zinc concentration in EPS in the diagnosis and treatment of prostatitis.