DataSheet1_Comprehensive Analysis of TRP Channel-Related Genes for Estimating the Immune Microenvironment, Prognosis, and Therapeutic Effect in Patients With Esophageal Squamous Cell Carcinoma.xlsx

The Nobel Prize in Physiology or Medicine for the year 2021 was awarded to Ardem Patapoutian and David Julius for their discoveries of temperature-sensitive receptors (TRP channels) and tactile receptors (Piezo channels), both of which were previously unknown. TRP channels are at the heart of the human ability to detect temperature, and they also play crucial regulatory functions in the occurrence and progression of cancer. Despite this, there have been no research conducted on the prognostic significance of TRP channels in individuals with esophageal squamous cell carcinoma (ESCC). In GEO and TCGA cohorts, unsupervised clustering was first conducted based on 18 TRP channel-associated differentially expressed genes (DEGs) extracted from MSigDB database and KEGG database. Two TRP subtypes were identified and patients in subtype B had the best prognosis among the two subtypes. Significant differences in staging and grading existed among the different subtypes. In GEO cohort, univariate Cox analysis were performed to screen prognosis related genes. A TRP channel-related prognostic signature, which included 7 signature-related genes, was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were divided into a high-risk group and low-risk group by the median risk score. In GEO and TCGA cohorts, Receiver operating characteristic (ROC) curves, principal component analysis (PCA), and univariate and multivariate Cox regression were performed to confirm the validity of signature. Following a more in-depth study of the TME based on the risk signature, it was discovered that the high-risk group had higher immune cell infiltration and lower tumor purity, indicating a bad prognosis. Patients with high risk scores also had increased immune checkpoint expression, indicating that these patients may be more likely to benefit from immunotherapy than other patients. We also found that paclitaxel, cisplatin, and 5-fluorouracil displayed a better response in treating the low-risk score ESCC patients. This study also adopted GTEx and qRT-PCR to perform experimental verification processes. In summary, we identified a TRP channel-associated prognostic signature. This signature can predict prognosis and immune microenvironment in ESCC.

2021年诺贝尔生理学或医学奖授予阿尔登·帕塔普蒂安（Ardem Patapoutian）与戴维·朱利叶斯（David Julius），以表彰他们发现了温度敏感受体——瞬时受体电位通道（TRP channels）与触觉受体Piezo通道（Piezo channels），二者此前均未被学界认知。瞬时受体电位通道是人类感知温度的核心分子基础，同时在癌症的发生与进展中发挥关键调控作用。然而目前尚无针对TRP通道在食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）患者中预后价值的研究。本研究首先基于从分子特征数据库（MSigDB）与京都基因与基因组百科全书（KEGG）中提取的18个TRP通道相关差异表达基因（DEGs），在基因表达综合数据库（GEO）与癌症基因组图谱（TCGA）队列中开展无监督聚类分析，最终鉴定出两种TRP亚型，其中B亚型患者的预后优于另一亚型。不同亚型在肿瘤分期与分级上存在显著差异。在GEO队列中，本研究通过单因素Cox回归分析筛选预后相关基因，并借助最小绝对收缩和选择算子（LASSO）Cox回归构建了包含7个特征基因的TRP通道相关预后特征模型。以风险评分中位数为界，将患者分为高风险组与低风险组。在GEO与TCGA队列中，本研究通过受试者工作特征曲线（ROC）、主成分分析（PCA）以及单因素、多因素Cox回归验证了该预后特征的有效性。基于该风险特征对肿瘤微环境（TME）进行深入分析后发现，高风险组的免疫细胞浸润程度更高、肿瘤纯度更低，提示预后不良。高风险评分患者的免疫检查点表达水平更高，表明此类患者或较其他患者更能从免疫治疗中获益。此外，本研究还发现紫杉醇（paclitaxel）、顺铂（cisplatin）与5-氟尿嘧啶（5-fluorouracil）对低风险评分的ESCC患者展现出更好的治疗响应。本研究同时采用基因型组织表达数据库（GTEx）与实时定量聚合酶链反应（qRT-PCR）开展实验验证。综上，本研究鉴定出一种TRP通道相关预后特征模型，该模型可用于预测ESCC患者的预后与免疫微环境状态。