Analysis of the Prognostic Value of Immune Checkpoints in Gastric Adenocarcinoma

2021 Year in Review - Gastrointestinal Cancer

Comprehensive analysis of immune checkpoints in gastric adenocarcinoma finds ICOSLG and CD70 may serve as prognostic biomarkers for gastric cancer.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. There are limited treatment options for gastric cancer, which leads to a poor prognosis. In advanced gastric cancer, the overall survival (OS) rate is approximately 12 months. Although there are limited treatment options for patients with advanced gastric cancer, research demonstrates that immunotherapy based on immune checkpoint inhibition and surgery has therapeutic value. A recent review used data from the Cancer Genome Atlas database and Oncomine to determine the gene expression profile of 415 patients with gastric adenocarcinoma and to analyze gene mutation and drug sensitivity.

Most of the immune checkpoints analyzed in the study altered gene expression in gastric adenocarcinoma. It was found that immune checkpoint expression had links to drug sensitivity and drug resistance. Many mutations were found in the immune checkpoints associated with gastric cancer, with the top 6 mutated genes in the study being NECTIN2, CD86, CD80, HHLA2, VSIR, and CD273. Among the gene mutations were “missense_mutation,” “frame_shift_del,” “nonsense_mutation,” “in_frame_del,” “frame_shift_ins,” and “multi_hit.” The mutated immune checkpoints were associated with immune response, T-cell activation, Janus kinase/signal transducer and activator of transcription and tumor necrosis factor–mediated signaling pathways, and other functions involved in tumor progression, carcinogenesis, and tumor escape.

The investigators found that CD70, CD274, ICOSLG, LGALS9, and PVR may serve as prognostic biomarkers in gastric cancer as has been suggested in other types of cancers. They are also associated with OS, first progression, and post-progression survival in patients with gastric cancer. ICOSLG and CD70 along with patient age, pathological TNM stage, and radiation therapy were independent prognosis factors for patients with gastric cancer. Additionally, the immune checkpoints ICOSLG and CD70 were found to have a correlation with the immune cells that play roles in tumor immune infiltration, anticancer immunity, and prognosis.

Study limitations include a limited number of immune checkpoints analyzed during the study and the analysis being performed at a messenger RNA level, not a protein or gene level. ICOSLG and CD70 may serve as prognostic biomarkers for patients with gastric cancer.

Source: Shen K, Liu T. Comprehensive analysis of the prognostic value and immune function of immune checkpoints in stomach adenocarcinoma. Int J Gen Med. 2021;14:5807-5824.

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