Abstract:
Abnormal transient receptor potential (TRP) channel function interferes with intracellular calcium-based signaling and causes malignant phenotypes. However, the effects of TRP channel-related genes on hepatocellular carcinoma (HCC) remain unclear. This study aimed to identify HCC molecular subtypes and prognostic signatures based on TRP channel-related genes to predict prognostic risks. Unsupervised hierarchical clustering was applied to identify HCC molecular subtypes using the expression data of TRP channel-related genes. This was followed by a comparison of the clinical and immune microenvironment characteristics between the resulting subtypes. After screening for differentially expressed genes among subtypes, prognostic signatures were identified to construct risk score-based prognostic and nomogram models and predict HCC survival. Finally, tumor drug sensitivities were predicted and compared between the risk groups. Sixteen TRP channel-related genes that were differentially expressed between HCC and non-tumorous tissues were used to identify 2 subtypes. Cluster 1 had higher TRP scores, better survival status, and lower levels of clinical malignancy. Immune-related analyses also revealed higher infiltration of M1 macrophages and higher immune and stromal scores in Cluster 1 than in Cluster 2. After screening differentially expressed genes between subtypes, 6 prognostic signatures were identified to construct prognostic and nomogram models. The potential of these models to assess the prognostic risk of HCC was further validated. Furthermore, Cluster 1 was more distributed in the low-risk group, with higher drug sensitivities. Two HCC subtypes were identified, of which Cluster 1 was associated with a favorable prognosis. Prognostic signatures related to TRP channel genes and molecular subtypes can be used to predict HCC risk.
摘要:
瞬时受体电位(TRP)通道功能异常干扰细胞内钙基信号并引起恶性表型。然而,TRP通道相关基因对肝细胞癌(HCC)的影响尚不清楚.这项研究旨在确定基于TRP通道相关基因的HCC分子亚型和预后特征,以预测预后风险。使用TRP通道相关基因的表达数据,应用无监督分层聚类来识别HCC分子亚型。随后比较了所得亚型之间的临床和免疫微环境特征。在筛选亚型间差异表达基因后,确定预后特征,以构建基于风险评分的预后和列线图模型,并预测HCC的生存.最后,对肿瘤药物敏感性进行了预测,并在风险组之间进行了比较.在HCC和非肿瘤组织之间差异表达的16个TRP通道相关基因用于鉴定2种亚型。第1组TRP得分较高,更好的生存状态,和较低水平的临床恶性肿瘤。免疫相关分析还显示,与第2组相比,第1组的M1巨噬细胞浸润更高,免疫和基质评分更高。在筛选亚型之间的差异表达基因后,确定了6个预后特征以构建预后和列线图模型。进一步验证了这些模型评估HCC预后风险的潜力。此外,集群1在低风险组中分布更多,具有较高的药物敏感性。确定了两个HCC亚型,其中第1组与良好的预后相关。与TRP通道基因和分子亚型相关的预后特征可用于预测HCC风险。