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The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma

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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.

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Abbreviations

ccRCC:

Clear cell renal cell carcinoma

GSEA:

Gene set enrichment analysis

TIMER:

Tumor immune estimation resource

ICB:

Immune checkpoint blockade

TIICs:

Tumor-infiltrating immune cells

HVEM:

Herpes virus entry mediator

SCNA:

Somatic copy number alteration

HR:

Hazard ratio

FDA:

Food and Drug Administration

DOR:

Duration of response

UISS:

University of California at Los Angeles Integrated Staging System

SSIGN:

Stage, size, grade, and necrosis

TCGA:

The Cancer Genome Atlas

TNFSF14:

TNF superfamily member 14

TMB:

Tumor mutation burden

OS:

Overall survival

LT-betaR:

Lymphotoxin-beta receptor

FDR:

False discovery rate

DEGs:

Differentially expressed genes

PD-1:

Programmed cell death 1

ORR:

Objective response rate

Tregs:

Regulatory T cells

MSKCC:

Memorial Sloan Kettering Cancer Center

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Acknowledgements

The authors would like to thank Dr. Xun Gong for providing statistical analysis assistance.

Funding

No funding was received.

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Authors and Affiliations

  1. Department of Medicine, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an, 710061, Shaanxi, China

    Fangshi Xu, Yibing Guan & Ke Gao

  2. Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, West Five Road, Xi’an, 710000, Shaanxi, China

    Peng Zhang, Li Xue, Xiaojie Yang & Tie Chong

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  1. Fangshi Xu
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  2. Yibing Guan
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  3. Peng Zhang
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  4. Li Xue
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  6. Ke Gao
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  7. Tie Chong
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Contributions

TC and FX were involved in the conception and design of the study. FX, YG and PZ performed data curation and statistical analysis. PZ, LX, FX, YG, XY and KG contributed to draft and reviewed this manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Tie Chong.

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Conflict of interest

Fangshi Xu, Yibing Guan, Peng Zhang, Li Xue, Xiaojie Yang, Ke Gao and Tie Chong declare that they have no conflict of interest.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Supplementary Figure

 1. Heat map of top 40 differentially expressed genes between high- and low-TMB groups. Upregulated genes are red; Downregulated genes are blue. (JPEG 443 kb)

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Xu, F., Guan, Y., Zhang, P. et al. The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma. Genes Genom 42, 1055–1066 (2020). https://doi.org/10.1007/s13258-020-00974-0

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