Development of anoikis-related genes signature to predict the prognosis in gastric cancer patients

Jie Cao; Kai Hong; Yuepeng Cao; Kenan Cen; Yifeng Mai; Ying Dai; Guifang Ouyang; Qitian Mu; Yangyang Guo

doi:10.3389/fonc.2022.1096608

Development of anoikis-related genes signature to predict the prognosis in gastric cancer patients

Front Oncol. 2023 Jan 12:12:1096608. doi: 10.3389/fonc.2022.1096608. eCollection 2022.

Authors

Jie Cao¹, Kai Hong², Yuepeng Cao², Kenan Cen³, Yifeng Mai³, Ying Dai³, Guifang Ouyang⁴, Qitian Mu¹, Yangyang Guo^{1

2}

Affiliations

¹ Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, China.
² Department of General Surgery, Ningbo First Hospital, Ningbo, China.
³ The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.
⁴ Department of Hematology, Ningbo First Hospital, Ningbo, China.

Abstract

Background: It is well known that the prognosis of Gastric cancer (GC) patient is affected by many factors. However, the latent impact of anoikis on the prognosis of GC patients is insufficient understood.

Methods: According to the Cancer Genome Atlas (TCGA) database, we elected discrepantly expressed anoikis-related genes (ARGs). Univariate cox and the least absolute shrinkage and selection operator (lasso) analysis were applied to build the ARGs signature. The prognostic effect of the ARGs signature was also evaluated. A series of algorithms were performed to evaluate the discrepancies in the immune microenvironment. Moreover, the correlation between drug sensitivity and ARGs signature was analyzed. We also performed Real-Time Polymerase Chain Reaction (RT-PCR) to probe the signature.

Results: The ARGs signature of 9 genes was constructed, which was apparently interrelated with the prognosis. The nomogram was established by combining the ARGs signature with clinicopathological characteristics. We found that the predictive power was noteworthily superior to other individual predictors. The immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, StromalScores, tumor immune dysfunction and exclusion (TIDE) score were lower in the low-risk group, while immunophenoscore (IPS) was on the contrary. The infiltrated immune cells and immune checkpoint (ICP) expression levels were significantly different between the two groups. Furthermore, nine drugs were positively associated with the ARGs signature score. The results of RT-PCR analysis were consistent with our previous differential expression analysis.

Conclusion: The developed ARGs signature could act as the biomarker and provide a momentous reference for Individual therapy of GC patients.

Keywords: anoikis; gastric cancer; immune microenvironment; immunotherapy; prognosis.

Grants and funding

This study was supported by the Ningbo Natural Science Fund (2019A610335), Zhejiang Province Medical Project (2020KY248), the Ningbo University Institute of Geriatrics (LNBYJS-2021), Ningbo Public Welfare Science and Technology Project (202002N3163), Zhejiang Province Traditional Chinese Medicine Project (2020ZB214) and Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province (2022E10026).