Abstract
BackgroundFamily with sequence similarity 57 member A (FAM57A) is a membrane associated gene contributing to lung carcinogenesis. In hepatocellular carcinoma (HCC) and other cancers, whether FAM57A exerts similar roles has been rarely reported. Herein, the biological functions and clinical significance of FAM57A in HCC were explored.MethodsInitially the differential expression of FAM57A between nontumor and HCC tissues was validated using a number of publicly accessible databases and immunohistochemistry (IHC). Then, the Kruskal–Wallis rank sum test or the Wilcoxon rank sum test as well as logistic regression were employed to analyze the association of FAM57A expression with clinical characteristics of HCC. The Cox regression and Kaplan–Meier analyses were conducted to assess the prognostic significance. Besides, with the coexpression analysis, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the molecular pathomechanisms that were mediated by FAM57A in HCC were elucidated. Furthermore, the correlations between FAM57A expression and tumor-infiltrating immune cells (TIICs) or immune checkpoint genes were analyzed. Finally, in vitro cell functional assay was carried out to preliminarily verify the role of FAM57A in HCC.ResultsFAM57A expression was demonstrated to be higher in HCC samples than in nontumor samples (all p-values <0.05), statistically correlated with clinicopathological characteristics (clinical stage, T stage, pathological grade), and inversely correlated to HCC patient survival. Univariate and multivariate Cox regression analyses showed that FAM57A expression could independently predict prognosis in HCC patients. Functional enrichment analyses further indicated that FAM57A was involved in multiple tumor-related pathways. FAM57A expression was positively correlated with TIICs, gene markers of TIICs, as well as immune checkpoint genes. Also, high expression of FAM57A predicted a poor prognosis for HCC based on immune cell subgroups. Functional assay of FAM57A knockdown significantly inhibited cell proliferation and induced cell apoptosis in HCC cells.ConclusionsOur results indicated that FAM57A could be used as a biomarker to predict the prognosis and immunotherapy response for HCC patients and might function as an oncogene to promote HCC progression.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide [1]
The results of 30 paired HCC/noncancerous IHC stained tissues from our hospital further confirmed the high protein expression level of Family with sequence similarity 57 member A (FAM57A) in tumor tissues (76.7% vs 46.7%, p
The diagnostic performance of FAM57A expression was not inferior to AFP in HCC patients based on the The Cancer Genome Atlas (TCGA) database (Figure 2E)
Summary
Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide [1]. Bioinformatics analysis and analysis of gene expression have elucidated the pathomechanism of certain cancers, revealing biomarkers for predicting prognosis and potentiating drug discovery and development [4, 5]. FAM57A has been demonstrated to activate the PI3K/Akt and Raf/Mek/Erk cascades and upregulate the expression of genes promoting metastasis in lung cancer cells [8]. These results indicated that FAM57A contributes to lung tumorigenesis. There have been reports that indicated FAM57A could play an oncogenic role in head and neck squamous cell cancer [9, 10]. In hepatocellular carcinoma (HCC) and other cancers, whether FAM57A exerts similar roles has been rarely reported. The biological functions and clinical significance of FAM57A in HCC were explored
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