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Low TIM3 expression indicates poor prognosis of metastatic prostate cancer and acts as an independent predictor of castration resistant status.

ABSTRACT: T cell immunoglobulin 3 (TIM3) is a cell surface star molecule expressed on T cells, and also marks dysfunctional CD8⁺ T cells in various kinds of cancers. However, there are few studies focusing on the expression of TIM3 in tumor cells. In our study, we recruited 139 patients with metastatic prostate cancer (mPCa) who received transurethral resection of the prostate (TURP) consecutively to examine whether TIM3 expression level is associated with overall survival (OS) in mPCa patients. Immunohistochemistry was performed to determine TIM3 expression in prostate cancer tissues and then patients were divided into two groups. In multivariate Cox analysis, we revealed that mPCa patients with negative TIM3 expression, younger age, no radiotherapy, higher Gleason score, higher cT stage and patients of mCRPC had a shorter OS. Therefore, a predictive nomogram was generated with identified independent prognostic factors to assess patients' OS at 3 years. Multivariate logistic regression revealed that higher cT stage, higher Gleason score and low TIM3 expression were independent predictors of metastatic castration resistant prostate cancer (mCRPC). In conclusion, low expression level of TIM3 in prostate cancer tissues is an independent prognostic factor of poor prognosis for mPCa patients, and also an independent predictor of mCRPC.

SUBMITTER: Wu J

PROVIDER: S-EPMC5567055 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Low TIM3 expression indicates poor prognosis of metastatic prostate cancer and acts as an independent predictor of castration resistant status.

Wu Junlong J Lin Guowen G Zhu Yao Y Zhang Hailiang H Shi Guohai G Shen Yijun Y Zhu Yiping Y Dai Bo B Ye Dingwei D

Scientific reports 20170821 1

T cell immunoglobulin 3 (TIM3) is a cell surface star molecule expressed on T cells, and also marks dysfunctional CD8<sup>+</sup> T cells in various kinds of cancers. However, there are few studies focusing on the expression of TIM3 in tumor cells. In our study, we recruited 139 patients with metastatic prostate cancer (mPCa) who received transurethral resection of the prostate (TURP) consecutively to examine whether TIM3 expression level is associated with overall survival (OS) in mPCa patients ...[more]

PMID: 28827755

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Project description:BackgroundHuman cell division cycle associated 8 (CDCA8) a key regulator of mitosis, has been described as a potential prognostic biomarker for a variety of cancers, such as breast, colon and lung cancers. We aimed to evaluate the potential role of CDCA8 expression in the prognosis of liver cancer by analysing data from The Cancer Genome Atlas (TCGA).MethodsThe Wilcoxon rank-sum test was used to compare the difference in CDCA8 expression between liver cancer tissues and matched normal tissues. Then, we applied logistic regression and the Wilcoxon rank-sum test to identify the association between CDCA8 expression and clinicopathologic characteristics. Cox regression and the Kaplan-Meier method were used to examine the clinicopathologic features correlated with overall survival (OS) in patients from the TCGA. Gene set enrichment analysis (GSEA) was performed to explore possible mechanisms of CDCA8 according to the TCGA dataset.ResultsCDCA8 expression was higher in liver cancer tissues than in matched normal tissues. Logistic regression and the Wilcoxon rank-sum test revealed that the increased level of CDCA8 expression in liver cancer tissues was notably related to T stage (OR = 1.64 for T1/2 vs. T3/4), clinical stage (OR = 1.66 for I/II vs. III/IV), histologic grade (OR = 6.71 for G1 vs. G4) and histological type (OR = 0.24 for cholangiocarcinoma [CHOL] vs. hepatocellular carcinoma [LIHC]) (all P-values < 0.05). Kaplan-Meier survival analysis indicated that high CDCA8 expression was related to a poor prognosis in liver cancer (P = 2.456 × 10-6). Univariate analysis showed that high CDCA8 expression was associated with poor OS in liver cancer patients, with a hazard ratio (HR) of 1.85 (95% confidence interval [CI]: 1.47-2.32; P = 1.16 × 10-7). Multivariate analysis showed that CDCA8 expression was independently correlated with OS (HR = 1.74; CI: 1.25-12.64; P = 1.27 × 10-5). GSEA revealed that the apoptosis, cell cycle, ErbB, MAPK, mTOR, Notch, p53 and TGF-β signaling pathways were differentially enriched in the CDCA8 high expression phenotype.ConclusionsHigh CDCA8 expression is a potential molecular predictor of a poor prognosis in liver cancer.

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Low TIM3 expression indicates poor prognosis of metastatic prostate cancer and acts as an independent predictor of castration resistant status.

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Low TIM3 expression indicates poor prognosis of metastatic prostate cancer and acts as an independent predictor of castration resistant status.

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