High SPATA18 Expression and its Diagnostic and Prognostic Value in Clear Cell Renal Cell Carcinoma.

BACKGROUND SPATA18 (spermatogenesis-associated 18, also called Mieap) encodes a protein that can induce lysosome-like organelles within mitochondria, which plays an important role in tumor growth. We measured the expression of SPATA18 in ccRCC, and assessed its diagnostic and prognostic clinical value in patients with clear cell renal cell carcinoma (ccRCC). MATERIAL AND METHODS We analyzed SPATA18 expression using data from the TCGA-KIRC cohort, GEO database, and UALCAN database. Immunohistochemistry was carried out to verify the expression in the ccRCC patients. The diagnostic value of SPATA18expression was evaluated by a receiver operating characteristic (ROC) curve. The correlation between clinical characteristics and SPATA18 expression was calculated by chi-square test. The prognostic value of SPATA18 expression was assessed by Kaplan-Meier analysis and Cox analysis. We conducted gene set enrichment analysis (GSEA) using TCGA database. RESULTS SPATA18 gene exhibited a higher expression in ccRCC tissues than in normal tissues. SPATA18 showed a substantial diagnostic value in ccRCC. SPATA18 expression was correlated with histological grade, clinical stage, T classification, and distant metastasis of ccRCC. Furthermore, high SPATA18 expression was associated with favorable overall survival. Multivariate analysis showed that SPATA18 was an independent risk factor for ccRCC. Gene set enrichment analysis (GSEA) showed that B cell receptors, WNT targets, extracellular matrix, oxidative phosphorylation, calcium metabolism, iron uptake and transport, potassium channels, and insulin receptor were differently enriched in the phenotype that was negatively correlated with SPATA18. CONCLUSIONS Our study indicated that high SPATA18 expression in ccRCC was associated with a good prognosis, and it could be a positive prognostic biomarker for ccRCC.

Risk factors and stratification of clinical significant prostate cancer in biopsy-naive patients with nonsuspicious multiparametric MRI / 中华泌尿外科杂志

Objective:To explore independent risk factors and risk stratification for diagnosis of clinically significant prostate cancer (CsPCa) in biopsy-naive patients with nonsuspicious multiparametric magnetic resonance imaging (mpMRI).Methods:The data of 549 patients who underwent initial systematic biopsy (SB) in the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Traditional Chinese Medicine Hospital of Kunshan between October 2015 and January 2021 were retrospectively reviewed. Nonsuspicious mpMRI was defined as Prostate Imaging-Reporting and Data System (PI-RADS)≤2. All patients received systematic 12 core prostate biopsy, 278 of them by transperineal and 271 by transrectal biopsies. The median age of the patients was 67 (62, 73) years, the median prostate specific antigen (PSA) was 9.01 (6.15, 13.64) ng/ml, the median prostate volume was 48.41 (35.85, 64.28) ml, and 54 patients were positive in digital rectal examination (DRE). Taking CsPCa as the outcome index, receiver operating characteristic (ROC) analysis was performed on age, tPSA, f/tPSA and PSA density (PSAD) to obtain the optimal cut-off value, and logistics regression was used to explore the independent risk factor of CsPCa in mpMRI negative patients. The optimal cut-off value when the negative predictive value (NPV) of mpMRI diagnosis of CsPCa was 100%, was taken as the protective factor, and the risk stratification model was finally proposed.Results:Of all 549 cases, 44 were CsPCa, 35 were clinically insignificant prostate cancer and 470 were non-prostate cancer. There were significant differences in age (71 vs. 67 years old), tPSA (11.95 vs. 8.75 ng/ml), PSAD [0.31 vs. 0.18 ng/(ml·cm 3)], f/tPSA (0.12 vs. 0.16) and DRE positive rate (38.6% vs. 7.3%) between CsPCa group and non-CsPCa group ( P<0.01). Cut-off values were taken in ROC analysis when the Youden index was at its maximum. The optimal cut-off values of each continuous variable were: age=65 years, tPSA=10ng/ml, f/tPSA=0.2 and PSAD=0.15 ng/(ml·cm 3). Multivariate analysis showed that ages over 65 years ( OR=3.43, 95% CI 1.55-7.58, P=0.002), f/t PSA ratio<0.2 ( OR=3.84, 95% CI 1.28-11.56, P=0.016), PSAD>0.15 ng/(ml·cm 3) ( OR=3.60, 95% CI 1.13-11.51, P=0.03) and positive DRE ( OR=5.20, 95% CI 2.39-11.32, P<0.001) were independent risk factors of CsPCa. When NPV was 100%, the cut-off values were taken as the protective factors: age≤55 years, f/tPSA≥0.3, PSAD≤0.1 ng/(ml·cm 3). Combined with independent risk factors, preliminary risk stratification was conducted: those with ≥2 high risk factors were considered as high risk group, those with ≥2 protective factors were considered as low risk group, and the middle region was considered as medium risk group. Conclusions:Patients with age>65 years, f/tPSA<0.2, PSAD > 0.15 ng/(ml·cm 3) and DRE positive are independent risk factors of CsPCa in mpMRI negative patients. Patients in the high-risk group were recommended to undergo prostate biopsy, while patients in the low-risk group could be considered to avoid biopsy.