Zhihui Jie

TIM-3 expression in tumor and stromal cells are associated with the prognosis in patients with epithelial ovarian cancer

T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) has been reported to be overexpressed and associated with poor prognosis in solid tumors. However, its features and prognostic value in epithelial ovarian cancer (EOC) remain undetermined. In this study, we aimed to characterize TIM-3 expression and its prognostic significance in patients with EOC. A total of 134 EOC patients and 20 healthy controls from North China were included. TIM-3 mRNA and protein expression in EOC tumor tissues and benign ovarian tissues were detected by real-time quantitative PCR and immunohistochemistry. The distribution of TIM-3 protein in different regions of EOC tissue (tumor cells and the tumor microenvironment) were evaluated by multicolor immunofluorescence. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. The results showed that high expression levels of TIM-3 mRNA were significantly associated with shorter progression-free survival (PFS; P  < .001, hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.29–1.91) and overall survival (OS; P  = .013, HR = 1.31, 95% CI = 1.06–1.63) durations in EOC patients. High TIM-3 expression levels in tumor cells had shorter PFS (HR = 1.62, 95% CI = 1.09–2.46, P  = .018) and OS (HR = 1.81, 95% CI = 1.19–2.75, P  = .006) compared with those low TIM-3 expression levels. Similarly, TIM-3 in the tumor microenvironment was also an independent factor that affected the clinical outcome of EOC patients (PFS: HR = 1.99, 95% CI = 1.29–3.08, P  = .002; OS: HR = 2.13, 95% CI = 1.37–.30, P  = .001). These findings indicated that IM-3 may be a potential biomarker for predicting prognosis and immunotherapy efficacy in patients with EOC, exerting different roles on tumor cells and tumor microenvironment.

Polymorphisms in miR-17-92 cluster promoter region is associated with risk and prognosis of endometrial cancer

Accumulating researches have reported that miR-17-92 cluster expression has strong association with tumorigenesis. In this study, we investigated the effects of 2 genetic polymorphisms in the promoter region of the miR-17-92 cluster and the risk and prognosis of endometrial cancer in northern Chinese women. Two polymorphisms (rs9588884 and rs982873) in the promoter of miR-17-92 cluster were genotyped by polymerase chain reaction and ligase detection reaction (PCR-LDR) in398 EC patients and 420 controls. The levels of miR-17-92 mRNA were investigated in 65EC tissues by real-time quantitative polymerase chain reaction (RT-qPCR). The impact of genetic features on the risk and clinical outcomes of EC was analyzed. The prognostic value of hsa-miR-17 and hsa-miR-20a in EC patients was assessed using the Kaplan–Meier plotter database. The results showed that a significant decrease in risk of EC with rs9588884 (GG vs CC: OR = 0.49, 95% CI = 0.32–0.78, P = .002; G vs C: OR = 0.75, 95% CI = 0.62–0.91, P = .005, respectively). Similarly, association was found between rs982873 and a decreased risk of EC (CC vs TT: OR = 0.53, 95% CI = 0.34–0.82, P = .004; C vs T: OR = 0.77, 95% CI = 0.63–0.94, P = .010, respectively). Moreover, survival analysis showed that the CG or GG genotype of rs9588884 may significantly increase overall survival (OS) compared with the CC genotype in the 5-year follow-up (HR = 0.49, 95% CI = 0.29–0.82 and HR = 0.36, 95% CI = 0.16–0.83, respectively). RT-qPCR results showed that the expression level of miR-17-92 mRNA in EC tissues with the rs9588884 GG genotype was significantly lower than those with the GC + CC genotype (P = .030). However, there was no significant difference in the prognosis and expression level of miR-17-92mRNA in tissues of EC patients with different genotypes of rs982873 (P = .343). In addition, analysis using Kaplan–Meier plotter database showed that high hsa-miR-20a expression was significantly correlated with poor OS in EC patients (HR = 1.63, 95% CI = 1.02–2.61, P = .039). The genetic polymorphisms rs9588884 and rs982873 in the promoter of miR-17-92 cluster decreased EC risk. Both rs9588884 and the expression level of hsa-miR-20a mRNA may be associated with its clinical outcome in EC patients.