ADAM۱۰: A Key Extracellular Matrix Gene Influencing Esophageal Cancer Survival

With the third highest death rate in the US, after colorectal, pancreatic, and hepatobiliary malignancies, esophageal cancer is the fourth most frequent gastrointestinal cancer. Iran is among the regions where esophageal cancer is known to occur often and according to an Iran Cancer Institute report, esophageal carcinoma includes approximately one-third of gastrointestinal cancers and one-tenth of all malignancies. The extracellular matrix (ECM) is closely associated with esophageal cancer’s pathogenesis and prognosis similar to other malignancies. Different ECM proteins confer different biochemical and biophysical properties that affect the cells’ microenvironment and vary the responses to therapeutic purposes. Our study aims to evaluate the survival and mortality rate of esophageal cancer connected with some ECM-related genes. Methods: ECM-associated gene sets were retrieved from the Molecular Signatures Database (MSigDB). These gene sets included important participants in signaling cascades, remodeling, and cell-matrix interactions. The gene sets were subjected to Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analysis to identify the prognostic genes based on their correlation with overall survival and ultimately. Additionally, patients with esophageal cancer were divided into low-risk and high-risk groups according to the median value of their risk ratings. The Kaplan-Meier plot was adopted to analyze the prognostic information of patient outcomes based on risk groups. The model's ability to discriminate was evaluated using Receiver Operating Characteristic (ROC) curves. Result: Based on Cox and LASSO regressions on gene sets, ultimately ADAM۱۰ was magnified, and the prognostic models were generated. According to survival analysis of ECSA the low-risk patient group had significantly better outcomes, while the high-risk group had a less favorable prognosis. The model's accuracy in predicting overall survival at one, two, and three years was further confirmed by ROC curves. Conclusion: We conducted this study to investigate the possible correlations between the expression of an ECM-related gene ADAM۱۰ and esophageal cancer survival. In broad terms, prognostic precision in ECSA is improved by understanding ECM-related gene dynamics. Our study will lead to better predictions in the course of disease and survival. In addition, these findings would expand the researchers' vision in personalized cancer management.

کلیدواژه ها:

Esophageal cancer ، Extracellular matrix ، Overall survival ، Prognosis