过表达干扰素诱导跨膜蛋白（IFITM）家族基因预示着肾透明细胞癌的预后不良。

Overexpressing IFITM family genes predict poor prognosis in kidney renal clear cell carcinoma.

作者信息

Xu Ying, Huang Danqi, Zhang Kun, Tang Zengqi, Ma Jianchi, Zhu Mansheng, Xiong Hui

机构信息

Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Transl Androl Urol. 2021 Oct;10(10):3837-3851. doi: 10.21037/tau-21-848.

DOI:10.21037/tau-21-848

PMID:34804826

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8575577/

Abstract

BACKGROUND

The interferon-inducible transmembrane (IFITM) proteins are localized in the endolysosomal and plasma membranes, conferring cellular immunity to various infections. However, the relationship with carcinogenesis remains poorly elucidated. In the present study, we investigated the role of IFITM in kidney renal clear cell carcinoma (KIRC).

METHODS

We utilized the online databases of Oncomine, UALCAN and Human Protein Atlas to analyze the expression of IFITMs and validate their levels in human KIRC cells by qPCR and western blot. Furthermore, we evaluated prognostic significance with the Gene Expression Profiling Interactive Analysis tool (Kaplan-Meier (KM) Plotter) and delineated the immune cell infiltration profile related to IFITMs with the TIMER2.0 database.

RESULTS

IFITMs were overexpressed in KIRC and varied in subtypes and tumor grades. High expression of IFITMs indicated a poor prognosis and more immune cell infiltration, especially endothelial cells and cancer-associated fibroblasts. IFITMs were associated with immune genes, which correlated with poor prognosis of renal clear cell carcinoma. We also explored the enriched network of IFITMs co-occurrence genes and their targeted transcription factors and miRNA. The expression of IFITMs correlated with hub mutated genes of KIRC.

CONCLUSIONS

IFITMs play a crucial role in the oncogenesis of KIRC and could be a potential surrogate marker for treatment response to targeted therapies.

摘要

背景

干扰素诱导跨膜蛋白（IFITM）定位于内溶酶体膜和质膜，赋予细胞对多种感染的免疫力。然而，其与肿瘤发生的关系仍未得到充分阐明。在本研究中，我们调查了IFITM在肾透明细胞癌（KIRC）中的作用。

方法

我们利用Oncomine、UALCAN和人类蛋白质图谱在线数据库分析IFITM的表达，并通过qPCR和蛋白质印迹法验证其在人KIRC细胞中的水平。此外，我们使用基因表达谱交互式分析工具（Kaplan-Meier（KM）绘图仪）评估预后意义，并使用TIMER2.0数据库描绘与IFITM相关的免疫细胞浸润谱。

结果

IFITM在KIRC中过表达，且在亚型和肿瘤分级中有所不同。IFITM的高表达表明预后不良和更多的免疫细胞浸润，尤其是内皮细胞和癌症相关成纤维细胞。IFITM与免疫基因相关，这与肾透明细胞癌的不良预后相关。我们还探索了IFITM共发生基因及其靶向转录因子和miRNA的富集网络。IFITM的表达与KIRC的枢纽突变基因相关。