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High expression of SIX1 is an independent predictor of poor prognosis in endometrial cancer.

ABSTRACT: Objective: The overexpression of transcription factor Sine oculis homeobox 1 (SIX1) is discovered in various malignant tumors and has been known to be closely associated with tumorigenesis, progression and prognosis. This study aims to determine the role of SIX1 in endometrial cancer (EC). Methods: In this study, we analyzed the SIX1 expression profile and the correlation with the corresponding clinical characteristics of EC samples from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases. Wilcoxon signed-rank test was applied to analyze the difference between tumor group and control group. The potential biological processes or signaling pathways related to SIX1 activity in EC was also assessed. Results: The results showed that SIX1 was overexpressed in EC tissues compared to normal tissues (P=2.029e-15, P=6.25e-6). The SIX1 level was correlated with tumor grade (P=2.91e-4), peritoneal cytology (P=0.005), and the subsequent tumor surgery (P=1.169e-4). SIX1 expression was negatively associated with overall survival rate (P=4.241e-4, P=0.000241) and served as an independent factor that affected EC overall survival rate (P=0.005063), similar to other factors such as age, Figo stage, and tumor (T) stage. SIX1 participates in cancer pathogenesis through gene regulation that involves PI3K/AKT/MTOR signaling, mitotic spindle, G2M checkpoint, E2F targets, NOTCH signaling, glycolysis, cholesterol homeostasis, DNA repair and early estrogen response. Conclusions: Our data demonstrate that SIX1 is overexpressed in EC and associated with adverse clinicopathological outcomes, which can function as an independent factor for EC prognosis.

SUBMITTER: Li W

PROVIDER: S-EPMC8129400 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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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High expression of SIX1 is an independent predictor of poor prognosis in endometrial cancer.

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