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Identification of potential biomarkers for endometrial carcinoma based on WGCNA

Lei Wang, Ying Ma,Zhe Liu,Yu Zhang, Xudong Liu,Yafan Wang, Lijun Zhao,Jinke Fan, Tao Peng,Rui Li,Yuxuan Chen,Xinqiang Song

Research Square (Research Square)(2022)

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摘要
Abstract Background Endometrial carcinoma (EC) is a group of malignant epithelial tumors occurring in the endometrium. With the increasing incidence of recent years, identifying the molecular mechanisms associated with endometrial carcinoma has become particularly important for the early diagnosis and treatment of cancer. Methods RNA-seq data and clinical information of patients were downloaded from The Cancer Genome Atlas (TCGA) database. In addition, functional enrichment analysis, differential expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were conducted. Next, hub genes associated with cancer progression were obtained by screening the module genes of interest, validated by survival analysis by GEPIA (p < 0.05). Finally, mutational analysis and immunohistochemistry validation were performed on the hub genes. Results We identified 3,308 genes with significant variants and screened them. And they were mainly associated with reproductive structure development, positive regulation of cytosolic calcium ion concentration, and cell − cell adhesion via plasma − membrane adhesion molecules. Weighted gene co-expression network analysis (WGCNA) identified six modules. By constructing a co-expression network, the turquoise module was found to be the most important module in predicting tumors. Apart from that, the turquoise module was negatively associated with cancer and was strongly correlated with patient weight, age, degree of tumor invasion and pregnancy status. Next, Survival analysis showed that NCMAP, ACTG2, TRPC1, RBMS3 are highly correlated with cancer progression. Finally, mutation analysis and IHC experiments further confirmed that TRPC1 plays a vital role in the occurrence and development of EC. Conclusion In summary, our research indicates that NCMAP, ACTG2, TRPC1, RBMS3 may play a central role in diagnosing and treating of endometrial carcinoma. TRPC1 may be a novel biomarker of the disease. These hub genes may provide a theoretical basis for targeted therapy against EC.
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关键词
endometrial carcinoma,potential biomarkers
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