The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma
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Genes & Genomics https://doi.org/10.1007/s13258-020-00974-0
RESEARCH ARTICLE
The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma Fangshi Xu1 · Yibing Guan1 · Peng Zhang2 · Li Xue2 · Xiaojie Yang2 · Ke Gao1 · Tie Chong2 Received: 30 March 2020 / Accepted: 14 July 2020 © The Genetics Society of Korea 2020
Abstract Background TNFSF14 has been proven to play an important role in various types of tumors. However, its function in renal cell carcinoma (RCC) has not yet been fully elucidated. Objective In order to explore molecular mechanism of RCC, we evaluated the effect of TNFSF14 on RCC progression, prognosis and immune microenvironment. Methods Using TCGA database, the differential expression of TNFSF14 and its relationships between clinicopathological features and prognosis were determined. Cox univariate and multivariate analyses were successively performed to identify whether TNFSF14 was an independent prognostic factor. The discriminating ability of TNFSF14 in RCC prognosis analysis was validated under the same clinical subgroups. Tumor mutational burden (TMB) of each RCC samples was calculated and the differential expression of TNFSF14 between high- and low-TMB groups was analyzed. The immune abundances of 22 leukocyte subtypes in each RCC samples were presented through the CIBERSORT algorithm. TIMER database was used to explore the relationships between copy number of TNFSF14 and the infiltration levels of 6 immune cells. Results Overexpression of TNFSF14 implied adverse clinicopathological features and poor prognosis. Meanwhile, TNFSF14 was identified as an independent prognostic factor (HR = 1.047, P = 0.028) and possessed prevalent applicability in RCC prognostic analysis. TNFSF14 was upregulated in high-TMB group than that in low-TMB group (Log2FC = 0.722). Moreover, overexpression of TNFSF14 brought alteration of immune abundance of 8 leukocyte subtypes. Besides, somatic copy number alteration (SCNA) of TNFSF14 was associated with infiltration levels of 6 immune cells. Conclusions TNFSF14 has crucial impact on progression, prognosis and immune microenvironment in RCC. Besides, TNFSF14 may be a potential biomarker for predicting the efficacy and response rate of RCC immunotherapy. Keywords TNFSF14 · Clear cell renal cell carcinoma · TCGA · Immunotherapy · Microenvironment · Tumor mutation burden · TIMER Abbreviations ccRCC Clear cell renal cell carcinoma GSEA Gene set enrichment analysis TIMER Tumor immune estimation resource ICB Immune checkpoint blockade Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13258-020-00974-0) contains supplementary material, which is available to authorized users. * Tie Chong [email protected] 1
Department of Medicine, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an 710061, Shaanxi, China
Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, West Five Road, Xi’an 710000, Shaanxi, China
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TIICs Tumor-infiltrat
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