Integrated Analysis of FAM57A Expression and Its Potential Roles in Hepatocellular Carcinoma

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.

Identification of HM13 as a prognostic indicator and a predictive biomarker for immunotherapy in hepatocellular carcinoma

“…These indicate that HM13 methylation is also involved in the occurrence and progression of HCC, which deserves more in-depth Importantly, our study expounded on the relationship between HM13 expression and TME in HCC. TIICs have been reported to play a key regulatory role in tumorigenesis and the progression of HCC [30][31][32]. We found a significant difference in the proportion of some TIICs between the HM13-high and HM13-low subgroups in TCGA.…”

FAM57A (Family with Sequence Similarity 57 Member A) Is a Cell-Density-Regulated Protein and Promotes the Proliferation and Migration of Cervical Cancer Cells

“…From these results, the question arises whether the functional inhibition of FAM57A may possess potential for cancer therapy, by blocking both cancer cell proliferation and migration. Studies reporting increased FAM57A expression in lung, liver, and head and neck cancers, when compared to the respective normal tissues [ 10 , 11 , 12 , 13 , 14 ], raise the possibility that there may exist a therapeutic window to preferentially target tumor cells. In this context, it is also thinkable that the hypoxia/HIF-1α-linked increase of FAM57A transcript levels observed in our study may contribute to their relative elevation in cancers, since cancers are typically more hypoxic [ 1 ] and often exhibit higher HIF-1α levels [ 49 ] than corresponding normal tissues.…”

“…FAM57A has also been linked to human carcinogenesis and both pro- and anti-tumorigenic activities have been described. For lung, liver, and head and neck cancers, FAM57A expression was reported to be increased in tumors compared to the corresponding normal tissues [ 10 , 11 , 12 , 13 , 14 ]. Interference with FAM57A expression in cell lines derived from lung and liver cancers acted anti-proliferative [ 12 , 13 , 14 ], suggesting a pro-tumorigenic role for FAM57A in these tumor entities.…”

“…For lung, liver, and head and neck cancers, FAM57A expression was reported to be increased in tumors compared to the corresponding normal tissues [ 10 , 11 , 12 , 13 , 14 ]. Interference with FAM57A expression in cell lines derived from lung and liver cancers acted anti-proliferative [ 12 , 13 , 14 ], suggesting a pro-tumorigenic role for FAM57A in these tumor entities. In contrast, FAM57A was reported to be a protective gene in prostate cancer in that FAM57A transcript levels were lower in tumorous than in normal prostate tissue, a decrease of FAM57A transcripts correlated with increased prostate cancer grading, and FAM57A silencing weakly enhanced the viability of LnCAP prostate cancer cells [ 15 , 16 ].…”