Establishment of an endoplasmic reticulum stress-related signature predicting outcomes of gastric adenocarcinoma patients

Background: Gastric adenocarcinoma (GAC) is a common clinical malignancy with a poor prognosis. Endoplasmic reticulum (ER) stress plays important roles in the progression, immune filtration, and chemoresistance of cancers. However, whether ER stress-related gene signatures can predict the prognosis of GAC patients remains unknown. Methods: GAC patient RNA-seq data downloaded from The Cancer Genome Atlas and gastric cancer patient microarray data from Gene Expression Omnibus datasets were analyzed using LASSO regression to construct an ER stress-related signature. Survival analysis, time-dependent receiver operating characteristic (ROC) curves, and Cox regression analysis were used to verify the efficacy of the signature. Immune infiltration, somatic mutation, immune checkpoint, and copy number variation analyses were utilized to explore the potential biological significance of the signature. Results: In the present study, eight ER stress-related gene signatures were constructed. Survival analysis showed that patients in the high-risk group had a significantly worse prognosis. The area under the time-dependent ROC curves was 0.65, 0.70, and 0.63 at 1, 3, and 5 years, respectively, in the training cohort. Cox regression analysis showed that the signature is an independent prognostic factor. To predict GAC patients' prognosis meeting individual needs, a nomogram was constructed with good accuracy. In addition, gene set enrichment and immune infiltration analyses showed that the ER stress-related signature is associated with cancer-related pathway activation and an immunosuppressive tumor microenvironment in GAC. Conclusion: In the current study, we established an ER stress-related signature. This prognostic signature has good predictive power and could facilitate the development of novel strategies for the clinical treatment of GAC.