Prognostic biomarker SMARCC1 and its association with immune infiltrates in hepatocellular carcinoma

Cancer Cell International

Jingwen Deng¹  Jiaming Zhou²  Xiaopeng Cai²  Zhi Chen² 

[1] Key Laboratory of Disease Proteomics of Zhejiang Province, Department of Pathology, Zhejiang University School of Medicine, 310058, Hangzhou, China;Women’s Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, China;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 310003, Hangzhou, China;

关键词: SMARCC1;    HCC;    Survival;    Hub genes;    Immune infiltrations;    Therapeutic target;   

DOI  :  10.1186/s12935-021-02413-w

来源: Springer

【 摘 要 】

BackgroundEpigenetic alterations contribute greatly to metastasis and dissemination in hepatocellular carcinoma (HCC). SMARCC1, as a SWI/SNF chromatin remodeling factor, has been reported to play important roles in many cancers. For the first time, with the bioinformatics analysis and wet-bench experiments, we explored the biological significance of SMARCC1 and its potential as putative therapeutic target in HCC.MethodsThe mRNA expression profiles and prognostic value of SMARCC1 were analyzed in the Oncomine, UALCAN and Kaplan–Meier Plotter databases. The expression of SMARCC1 and associated clinicopathological factors were further evaluated using a tissue microarray. Differentially expressed genes associated with SMARCC1 in HCC were obtained and analyzed via the LinkedOmics and GEPIA databases and Cytoscape software. To verify the important role of SMARCC1 in HCC, we knocked down and overexpressed SMARCC1 in different hepatic cell lines and conducted several functional experiments. Then, we evaluated the mutation profiles and transcriptional regulators of SMARCC1 using the cBioPortal, COSMIC, CistromeDB and TCGA databases. Finally, we addressed the relationship of SMARCC1 expression with immune cell infiltration via TIMER database analysis.ResultsThrough data mining and tissue microarray verification, we found that the protein and mRNA levels of SMARCC1 are high in tumor tissues, which has remarkable diagnostic value in HCC patients. SMARCC1 and its hub genes showed prognostic value in HCC. Furthermore, we confirmed that SMARCC1 influenced the proliferation, migration, and invasion of HCC cells. Moreover, correlation analyses revealed that SMARCC1 expression was positively correlated with ZBTB40 transcription factors and negatively correlated with the DNA methylation level. Overall, we found that SMARCC1 affects immune infiltration and plays a tumor-promoting role in HCC.ConclusionsSMARCC1 is overexpressed and is a putative prognostic predictor in HCC. Due to the tumor-promoting role of SMARCC1, treatments inhibiting DNA methyltransferases and transcription factors or weakening the role of SMARCC1 in immune infiltration might improve the survival of HCC patients.

【 授权许可】

CC BY