Vol.45, No.3, 2021, pp.589-597, doi:10.32604/biocell.2021.013882
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ARTICLE
Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma
  • MENGDAN WU1, MENGYAO SUN1, QINHUAI LAI1, YIN LU1, YUYIN FU1, YUJIA PENG1, WEIRONG LAI1, LISHI ZENG1, SHENGYAN ZHAO1, YUYAN LI1, ZHIXIONG ZHANG1, XIAOFENG CHEN1, FAN QIAO1, YIWEN ZHANG1,*, SHIJIE ZHOU1,2,*, LANTU GOU1, JINLIANG YANG1,2
1 Department of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
2 Guangdong Zhongsheng Pharmaceutical Co., Ltd., Shantou, 515041, China
* Address correspondence to: Yiwen Zhang, ; Shijie Zhou,
Received 27 August 2020; Accepted 05 November 2020; Issue published 03 March 2021
Abstract
The chemokine ligand 13-chemokine receptor 5 (CXCL13-CXCR5) axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment (TME) in multiple types of solid tumors. In this study, we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma (KIRC) and its correlation with tumor-infiltrating immune cells (TIICs). A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry (IHC). Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas (TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB. Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). KIRC cell lines, as well as several other cancer cell lines, had negative CXCL13 expression. IHC staining from the Human Protein Atlas (HPA) and our tissue array indicated that CXCL13 might be mainly expressed by TIICs, but not KIRC tumor cells. CXCL13 expression was strongly and positively correlated with γδ T cell abundance in TME. Besides, γδ T cell infiltration was associated with poor survival of KIRC. Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs. The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription. In conclusion, our study revealed that CXCL13 expression and γδ T cell infiltration in TME is associated with unfavorable survival of KIRC. TIICs, most possibly γδ T cells, are the dominant source of CXCL13 in KIRC TME.
Keywords
CXCL13, Kidney clear cell carcinoma, Gamma/delta T cells, DNA methylation, Unfavorable survival
Cite This Article
WU, M., SUN, M., LAI, Q., LU, Y., FU, Y. et al. (2021). Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma. BIOCELL, 45(3), 589–597.
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