Guo Yang, Liu Ning
Shenyang Tenth People's Hospital (Shenyang Chest Hospital), No 11 Beihai Street, Dadong District, Shenyang 110044, Liaoning, China.
J Oncol. 2022 Aug 31;2022:5388283. doi: 10.1155/2022/5388283. eCollection 2022.
Transient receptor potential channel (TRP) is a superfamily of nonselective cation channels, which is a member of calcium ion channels with a vital role in different calcium ion signal transduction pathways. TRP channel expression is often changed in the tumor, although the role of TRP proteins in lung cancer is unknown.
Molecular Signatures Database (MsigDB) provided the TRP gene set. Univariate Cox regression analysis was performed on The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) data collection set employing the coxph function of R package survival to find prognosis-related genes. The R package ConsumusClusterPlus was employed for doing the consistency cluster analysis of TCGA-LUAD samples according to the prognosis-related TRP gene. The R-package limma was utilized for investigating the differential expression of TRP subtypes. According to the differentially expressed genes between subtypes, the least absolute shrinkage and selection operator (LASSO) regression was employed to find the major genes and develop the risk model. CIBERPORT algorithm, R package maftools, gene set variation analysis (GSVA), and pRRophetic of R-package were employed for measuring the proportion of immune cells among subtypes, genomic mutation difference, pathway enrichment score, and drug sensitivity analysis.
A total of 15 TRP-related genes associated with the prognosis of lung adenocarcinoma were found. According to the expression value of 15 genes, lung adenocarcinoma can be sorted into two subcategories. The prognosis of cluster1 is considerably better in comparison with that of cluster2. There were 123 differentially expressed genes between C1 and C2 subtypes, including 6 up- and 117 downregulated genes. There were major variations in the tumor microenvironment between C1 and C2 subtypes. The proportion of CD8 T cells in the C1 subtype was considerably enhanced in comparison with that in the C2 subtype. We further discovered 123 differentially expressed genes among subtypes, and 8 key genes were obtained at the end. The risk score (RS) model developed by the 8-gene signature had good strength in the TCGA validation set, overall set, and Gene Expression Omnibus (GEO) external dataset. There were major variations in immune checkpoint gene expression, patient sensitivity to immunotherapeutic drugs, immune infiltration, and genomic mutations between high and low groups on the basis of RS.
The risk model developed on the basis of TRP-related genes can help in predicting the prognosis of patients suffering from lung adenocarcinoma and guide immunotherapy.
瞬时受体电位通道（TRP）是一类非选择性阳离子通道超家族，是钙离子通道的成员之一，在不同的钙离子信号转导途径中起重要作用。TRP通道表达在肿瘤中常发生改变，尽管TRP蛋白在肺癌中的作用尚不清楚。
分子特征数据库（MsigDB）提供TRP基因集。利用R包survival的coxph函数对癌症基因组图谱肺腺癌（TCGA-LUAD）数据集进行单变量Cox回归分析，以寻找预后相关基因。使用R包ConsumusClusterPlus根据预后相关的TRP基因对TCGA-LUAD样本进行一致性聚类分析。利用R包limma研究TRP亚型的差异表达。根据亚型间的差异表达基因，采用最小绝对收缩和选择算子（LASSO）回归寻找主要基因并建立风险模型。采用CIBERPORT算法、R包maftools、基因集变异分析（GSVA）和R包的pRRophetic来测量亚型间免疫细胞比例、基因组突变差异、通路富集分数和药物敏感性分析。
共发现15个与肺腺癌预后相关的TRP相关基因。根据15个基因的表达值，肺腺癌可分为两个亚类。与cluster2相比，cluster1的预后明显更好。C1和C2亚型之间有123个差异表达基因，包括6个上调基因和117个下调基因。C1和C2亚型之间的肿瘤微环境存在主要差异。与C2亚型相比，C1亚型中CD8 T细胞的比例显著增加。我们进一步发现亚型间有123个差异表达基因，最终获得8个关键基因。由8基因特征建立的风险评分（RS）模型在TCGA验证集、总体集和基因表达综合数据库（GEO）外部数据集中具有良好的预测能力。基于RS的高低分组在免疫检查点基因表达、患者对免疫治疗药物的敏感性、免疫浸润和基因组突变方面存在主要差异。
基于TRP相关基因建立的风险模型有助于预测肺腺癌患者的预后并指导免疫治疗。
