Fam198b as a novel biomarker for gastric cancer and a potential therapeutic target to prevent tumor cell proliferation dysregulation

Highlights

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  Increased Fam198b expression in GC is associated with poor prognosis.

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  The function of Fam198b in gastric cancer was testified by bioinformatics and in vitro experiments.

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  Fam198b promoted the proliferation, migration and invasion of gastric cancer cell lines.

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  Fam198b regulates Bcl-2 expression through the classical PI3K/AKT pathway to promote GC progression.

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  Fam198b is a novel biomarker for gastric cancer and a potential therapeutic target to prevent dysregulated tumor cell proliferation.

Abstract

Background

It has been reported that the human family with sequence similarity 198, member B (Fam198b) play an important role in the occurrence and development of various cancers. Nevertheless, its function in gastric cancer is not completely clear. Hereby, we investigated the function and prognostic value of Fam198b in gastric cancer and further validated the results in gastric cancer through a series of in vitro experiments.

Methods

We used R software and online bioinformatics analysis tools-GEPIA2, TIMER2, Kaplan-Meier plotter, cBioPortal, TISIDB COSMIC, and STRING to study the characteristics and functions of Fam198b in GC, such as aberrant expression, prognostic value, genomic alterations, immune microenvironment, anticancer drug sensitivity, and related signaling pathways. In addition, in vitro experiments such as immunohistochemistry (IHC), cell function experiments, and signaling pathway experiments were performed to validate the key conclusions.

Result

Fam198b is obviously highly expressed in gastric cancer, and its expression is intensively correlated with tumor prognosis. The etiology of abnormal Fam198b expression was superficially investigated and validated by associating genomic alterations and the immune microenvironment. Furthermore, Fam198b is intensively correlated with the sensitivity of multiple antitumor drugs. It was demonstrated by functional enrichment analysis that Fam198b was linked to myogenesis, angiogenesis, epithelial mesenchymal transition and cytokine binding. It was observed in vitro experiments that knockdown Fam198b could significantly inhibit tumor cell proliferation and migration. These results were reversed when Fam198b was overexpressed. It was validated by signaling pathway experiments that Fam198b promoted gastric cancer progression by up-regulating the PI3K/AKT/BCL-2 signaling pathway.

Conclusion

As a novel biomarker to predict GC prognosis and tumor progression, Fam198b is a promising therapeutic target to reverse tumor progression.