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

Bangquan Chen; Maladho Tanta Diallo; Yue Ma; Wenhao Yu; Qing Yao; Shuyang Gao; Yantao Yu; Qiannan Sun; Yong Wang; Jun Ren; Daorong Wang

doi:10.1016/j.tranon.2023.101824

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

Transl Oncol. 2024 Jan:39:101824. doi: 10.1016/j.tranon.2023.101824. Epub 2023 Nov 6.

Authors

Bangquan Chen¹, Maladho Tanta Diallo¹, Yue Ma², Wenhao Yu¹, Qing Yao³, Shuyang Gao³, Yantao Yu³, Qiannan Sun⁴, Yong Wang⁴, Jun Ren⁵, Daorong Wang⁶

Affiliations

¹ Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, PR China; General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, PR China; Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, PR China.
² Northern Jiangsu People's Hospital , Medical School of Nanjing University, Yangzhou 225001, PR China; General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, PR China; Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, PR China.
³ Northern Jiangsu People's Hospital Affiliated to Dalian Medical University, Yangzhou 225001, PR China; General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, PR China; Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, PR China.
⁴ Northern Jiangsu People's Hospital, Yangzhou 225001, PR China; General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, PR China; Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, PR China.
⁵ Northern Jiangsu People's Hospital, Yangzhou 225001, PR China; Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, PR China; General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, PR China; Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, PR China. Electronic address: freezingfall@163.com.
⁶ Northern Jiangsu People's Hospital, Yangzhou 225001, PR China; Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, PR China; General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, PR China; Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, PR China. Electronic address: wdaorong666@sina.com.

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.

Keywords: Biomarker; Fam198b; Gastric Cancer; PI3K/Akt; Prognosis; TCGA.