Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

Abstract

Background An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS‐related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. Methods The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients’ sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein–protein interaction (PPI) network and their expression was validated using clinical specimens. Results A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low‐risk group had a lower IC50 for the common chemotherapy drug, 5‐FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. Conclusion We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

“…Expression of XBP1s promotes the proliferation of colon cancer cells (Liu et al 2023 ). In a risk model of ER stress-related genes (ERSRGs) for prognostic assessment and treatment of CRC patients, the high-risk group was shown to be more resistant to the chemotherapeutic agent 5-Fluorouracil (5-FU), and risk scores were positively correlated with 5-FU resistance(Geng et al 2023 ). ATF6 expression is detected in colorectal cancer but is absent in normal colonic mucosa.…”

Compound 225# inhibits the proliferation of human colorectal cancer cells by promoting cell cycle arrest and apoptosis induction

“…It has been demonstrated that cell cycle arrest depends on the activation of DNA damage signaling pathways, which also influence the proliferation of cancer cells ( 5 ). Previous studies have reported that selectively targeting specific biomarkers involved in the regulation of cell division or apoptosis can have a significant impact on tumor growth or the supportive environment of cancer cells, while having minimal influence on normal cells ( 6 – 8 ). The identification of compounds that can inhibit the cell cycle and induce apoptosis shows promise in the development of potential drugs for CRC therapy.…”