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泛癌分析揭示了TRPV通道相关基因的基因组和临床特征。

Pan-Cancer Analysis Reveals Genomic and Clinical Characteristics of TRPV Channel-Related Genes.

作者信息

Wang Xiaoxuan, Li Guanghao, Zhang Yidan, Li Lanfang, Qiu Lihua, Qian Zhengzi, Zhou Shiyong, Wang Xianhuo, Li Qiang, Zhang Huilai

机构信息

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.

Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

出版信息

Front Oncol. 2022 Jan 31;12:813100. doi: 10.3389/fonc.2022.813100. eCollection 2022.

DOI:10.3389/fonc.2022.813100
PMID:35174089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8841404/
Abstract

BACKGROUND

Transient Receptor Potential channels (TRPs), a class of ion channels, were first described two decades ago. Many TRP family members are major participants in nociception and integration of heat and pain signals. Recent studies have revealed that subfamilies of this channel, such as members of transient receptor potential vanilloid (TRPV) channels, play important roles in breast, ovarian, prostate, and pancreatic cancers.

METHODS

We performed a comprehensive analysis of TRPVs in 9125 tumor samples of 33 cancer types using multi-omics data extracted from The Cancer Genome Atlas (TCGA). We identified differences in mRNA expression in a pan-cancer analysis, and the genomic characteristics of single nucleotide variations, copy number variations, methylation features, and miRNA-mRNA interactions using data from TCGA. Finally, we evaluated the sensitivity and resistance to drugs targeting TRPV channel-related genes using the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) database. Finally, we validated the drug sensitive data and the importance of TRPV6 in two cancer cell lines using q-PCR assay, CCK8 assay, EdU assay and scratch assay.

RESULTS

Extensive genetic alterations in TRPV channel-related genes and differences in gene expression were associated with the activity of cancer marker-related pathways. TRPV channel-related genes can be used as prognostic biomarkers. Several potential drugs, such as lapatinib, that may target TRPV channel-related genes were identified by mining the genomics of drug sensitivity.

CONCLUSION

This study revealed the genomic changes and clinical characteristics of TRPV channel-related regulatory factors in 33 types of tumors. This analysis may help uncover the TRPV channel-related genes associated with tumorigenesis. We also proposed novel strategies for tumor treatment.

摘要

背景

瞬时受体电位通道（TRPs）是一类离子通道，于二十年前首次被描述。许多TRP家族成员是伤害感受以及热和疼痛信号整合的主要参与者。最近的研究表明，该通道的亚家族，如瞬时受体电位香草酸（TRPV）通道成员，在乳腺癌、卵巢癌、前列腺癌和胰腺癌中发挥重要作用。

方法

我们使用从癌症基因组图谱（TCGA）中提取的多组学数据，对33种癌症类型的9125个肿瘤样本中的TRPVs进行了全面分析。我们在泛癌分析中确定了mRNA表达的差异，并利用TCGA的数据确定了单核苷酸变异、拷贝数变异、甲基化特征以及miRNA-mRNA相互作用的基因组特征。最后，我们使用癌症治疗反应门户（CTRP）和癌症药物敏感性基因组学（GDSC）数据库评估了针对TRPV通道相关基因的药物的敏感性和耐药性。最后，我们使用q-PCR检测、CCK8检测、EdU检测和划痕检测在两种癌细胞系中验证了药物敏感数据以及TRPV6的重要性。

结果

TRPV通道相关基因的广泛遗传改变和基因表达差异与癌症标志物相关途径的活性有关。TRPV通道相关基因可作为预后生物标志物。通过挖掘药物敏感性基因组学，确定了几种可能靶向TRPV通道相关基因的潜在药物，如拉帕替尼。

结论

本研究揭示了33种肿瘤中TRPV通道相关调节因子的基因组变化和临床特征。该分析可能有助于发现与肿瘤发生相关的TRPV通道相关基因。我们还提出了新的肿瘤治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffa1/8841404/8f54cb568379/fonc-12-813100-g008.jpg
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