食管鳞状细胞癌（ESCC）是最常见的恶性胃肠肿瘤。离子通道通过与其相邻的分子（包括脂质）相互作用，对肿瘤的生长和发展起到作用。膜离子通道和脂质代谢的失调可能导致上皮间质转化（EMT），从而引起转移性进展。本文通过进行差异基因表达和加权基因共表达网络分析，对ESCC患者的转录组进行了分析，以确定ESCC中的改变离子通道、脂质代谢和EMT相关基因。在ESCC患者中共鉴定出1,081个差异表达基因，其中包括113个离子通道、487个脂质代谢相关基因和537个EMT相关基因。随后，EMT评分与改变共表达基因之间进行了相关性分析，发现改变的共表达基因与EMT特征相关。使用蛋白质相互作用网络确定了22个离子通道与3个脂质代谢中心和13个EMT相关蛋白之间的相互作用。生成了一个通路图，描述了ESCC中失调的信号通路，如胰岛素抵抗和雌激素受体-Ca2+信号通路。使用Kaplan-Meier绘图和Cox比例风险回归分析确定了潜在离子通道与ESCC 5年生存率之间的关系。发现肌球蛋白调解通道1（GJA1）和肌苷酸5'三磷酸酯型受体3（ITPR3）与ESCC患者的不良预后有关。此外，还确定了与潜在离子通道（包括GJA1和ITPR3）相互作用的药物。了解ESCC病理生理学中离子通道、脂质代谢和EMT的变化，可能为ESCC患者的更好治疗提供潜在靶点。版权所有 © 2023 Parthasarathi, Mandal, George, Gaikwad, Sasidharan, Gundimeda, Jolly, Pandey and Sharma.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignant gastrointestinal tumor. Ion channels contribute to tumor growth and progression through interactions with their neighboring molecules including lipids. The dysregulation of membrane ion channels and lipid metabolism may contribute to the epithelial-mesenchymal transition (EMT), leading to metastatic progression. Herein, transcriptome profiles of patients with ESCC were analyzed by performing differential gene expression and weighted gene co-expression network analysis to identify the altered ion channels, lipid metabolism- and EMT-related genes in ESCC. A total of 1,081 differentially expressed genes, including 113 ion channels, 487 lipid metabolism-related, and 537 EMT-related genes, were identified in patients with ESCC. Thereafter, EMT scores were correlated with altered co-expressed genes. The altered co-expressed genes indicated a correlation with EMT signatures. Interactions among 22 ion channels with 3 hub lipid metabolism- and 13 hub EMT-related proteins were determined using protein-protein interaction networks. A pathway map was generated to depict deregulated signaling pathways including insulin resistance and the estrogen receptor-Ca2+ signaling pathway in ESCC. The relationship between potential ion channels and 5-year survival rates in ESCC was determined using Kaplan-Meier plots and Cox proportional hazard regression analysis. Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) was found to be associated with poor prognosis of patients with ESCC. Additionally, drugs interacting with potential ion channels, including GJA1 and ITPR3, were identified. Understanding alterations in ion channels with lipid metabolism and EMT in ESCC pathophysiology would most likely provide potential targets for the better treatment of patients with ESCC.Copyright © 2023 Parthasarathi, Mandal, George, Gaikwad, Sasidharan, Gundimeda, Jolly, Pandey and Sharma.