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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,
BIOCELL 2021, 45(3), 589-597. https://doi.org/10.32604/biocell.2021.013882
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
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. https://doi.org/10.32604/biocell.2021.013882
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