Abstract
Endoplasmic reticulum (ER) stress is a state in which misfolded or unfolded proteins accumulate in the lumen of the ER as a result of some exogenous or endogenous factors. It plays a crucial role in the pathogenesis of malignancies, affecting cell survival, proliferation, and metastasis in cancer. ER stress genes could provide new ideas for potential therapeutic targets in cancer. In our study, we aimed to construct an ER stress-related genes (ERGs) model for hepatocellular carcinoma (HCC). ERGs with differential expression and significant survival were screened to construct a prognostic model. The effectiveness of the model was successfully validated by external datasets. High and low-risk groups were classified based on risk scores. Functional analysis showed risk groups involved in the unfolded protein response, DNA repair, and other differential pathways. When compared to patients with low risk, the prognosis for HCC patients in the high-risk group might be worsened by disruptions in these pathways. Importantly, we considered genomic druggability and predicted drugs. Sorafenib-induced autophagy in HCC cells through an ES stress mechanism. Sorafenib was more sensitive for high-risk patients. In brief, our model predicted the prognosis of HCC and provided novel treatment strategies for the study of other cancers.