Exploration of hub genes, lipid metabolism, and the immune microenvironment in stomach carcinoma and cholangiocarcinoma

Yuda Gong; Xuan Liu; Arvind Sahu; Abhinav V Reddy; Haiyu Wang

doi:10.21037/atm-22-3530

Exploration of hub genes, lipid metabolism, and the immune microenvironment in stomach carcinoma and cholangiocarcinoma

Ann Transl Med. 2022 Aug;10(15):834. doi: 10.21037/atm-22-3530.

Authors

Yuda Gong¹, Xuan Liu¹, Arvind Sahu², Abhinav V Reddy³, Haiyu Wang¹

Affiliations

¹ Department of General Surgery, Fudan University Zhongshan Hospital, Shanghai, China.
² Department of Oncology, Goulburn Valley Health, Shepparton, Victoria, Australia.
³ Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Sidney Kimmel Cancer Center, Baltimore, MD, USA.

Abstract

Background: Gastric cancer (GC) is the 5th most common cause of cancer in the world and the 3rd largest cause of cancer-related death. It is usually associated with a variety of cancers, of which cholangiocarcinoma (CCA) combined with GC accounts for about 1.6%. This study sought to examine the hub genes and role of lipid metabolism in the development and diagnosis of GC and CCA.

Methods: To screen potential hub genes, The Cancer Genome Atlas (TCGA) data sets, including the GC (STAD, dataset of GC) and CCA (CHOL, dataset of CCA) data sets, were used to conduct a differentially expressed gene (DEG) analysis and an enrichment analysis of the DEGs. A weighted-gene co-expression network analysis (WGCNA) was conducted to identify the significant gene module and then find the hub genes in the module. To verify the 4 hub genes, we conducted a differentiation analysis of the 4 genes in GC and CCA and found that there were differences. A survival analysis of the hub genes was performed and mutations were mapped. Additionally, tumor immune microenvironment (TIME) and immune analyses were performed to evaluate how lipid metabolism affects the development of GC with CCA.

Results: The principal component analysis showed that both GC and CCA had distinct up-regulated and down-regulated genes, which are involved in a variety of metabolic processes. Upon WGCNA, the turquoise and blue modules were meaningful, and the hub genes were identified from these 2 modules. Four hub genes were identified: amyloid beta precursor protein binding family B member 1 (APBB1), Homo sapiens armadillo repeat containing X-linked 1 (ARMCX1), DAZ interacting zinc finger protein 1 (DZIP1), and methionine sulfoxide reductase B3 (MSRB3). In survival analysis, increased expression of the 4 hub genes was associated with inferior survival outcomes, with variations in all 4 genes. Additionally, we demonstrated that genes related to lipid metabolism had an effect on immune function.

Conclusions: APBB1, ARMCX1, DZIP1, and MSRB3 affect the development of GC and CCA and can be used as biomarkers. The expression of lipid metabolism genes is related to the TIME of patients with GC and CCA.

Keywords: Gastric carcinoma; cholangiocarcinoma (CCA); hub gene; lipid metabolism.