Gastric cancer is the fifth most common cancer and the third most common cause of cancer-related mortality globally.1 Adenocarcinoma is the most common type of gastric cancer, accounting for 90% to 95% of all cases.2 There are several risk factors associated with the development of gastric cancer, but the exact etiology is unknown.2 It is often diagnosed in advanced stages, with a survival rate of <1 year.2 Therapies for treatment of advanced gastric cancer are limited, but ongoing research demonstrates that immunotherapy based on immune checkpoint inhibition has therapeutic value.1 In the September 2021 International Journal of General Medicine, Dr Kai Shen and Dr Tong Liu published a comprehensive research article on the prognostic value and immune function of immune checkpoints in gastric adenocarcinoma. Using data from the Cancer Genome Atlas database and Oncomine, they determined the gene expression profile for 415 patients with gastric adenocarcinoma. Gene mutation and drug sensitivity were also analyzed. Results were verified using quantitative real-time polymerase chain reaction.
An analysis of 16 immune checkpoints revealed most were upregulated in gastric adenocarcinoma when compared with normal gastric tissue. Immune checkpoint expression was linked to drug sensitivity and drug resistance. When gene mutations were analyzed, many mutations were discovered. The top 6 mutated genes in the study tissue were NECTIN2, CD86, CD80, HHLA2, VSIR, and CD273. Gene mutations included missense_mutation, frame_shift_del, nonsense_mutation, in_frame_del, frame_shift_ins, and multi_hit. The altered immune checkpoints were associated with functions involved with tumor immune escape, carcinogenesis, and progression in gastric adenocarcinoma.
The analysis discovered CD70, CD274, ICOSLG, LGALS9, and PVR had an association with post-progression survival, overall survival, and first progression in gastric cancer. In addition, they may also serve as prognostic biomarkers in gastric and other types of cancer. When further univariate and multivariate analysis was performed during this study, it was found that ICOSLG, CD70, age, pTNM stage, and radiation therapy were independent prognosis factors for patients with gastric cancer. Furthermore, ICOSLG and CD70 were found to have a correlation with immune cells including macrophages, neutrophils, dendritic cells, CD8+ T-cells, and CD4+ T-cells, all of which play roles in anticancer immunity, tumor immune infiltration, and prognosis.
The researchers acknowledged several study limitations, including a limited number of immune checkpoints included in the study and the analysis being performed at an mRNA level and not at a protein or gene level.
References
- 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.
- National Cancer Institute. Esophageal cancer treatment (adult) (PDQ®)-health professional version. Updated July 15, 2021. www.cancer.gov/types/esophageal/hp/esophageal-treatment-pdq. Accessed October 3, 2021.