1. Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients
- Author
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Chunyan Zhao, Xiaoteng Cui, Nan Zhang, Jie Yang, Zhi Yao, Yuanyuan Ren, Chao Su, Shaoyuan Wu, and Xingjie Gao
- Subjects
0301 basic medicine ,China ,Cancer Research ,Carcinoma, Hepatocellular ,DNA Mutational Analysis ,Expression ,Biology ,Gene mutation ,medicine.disease_cause ,Pathologic stage ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Gene expression ,Genetics ,medicine ,Animals ,Humans ,Copy-number variation ,HCC ,Gene ,RC254-282 ,Neoplasm Staging ,Mutation ,Research ,Liver Neoplasms ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cohort ,Cancer research - Abstract
Background The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC. Methods Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model. Results We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases. Conclusions Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.
- Published
- 2021
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