@Article{biocell.2021.013882,
AUTHOR = {MENGDAN WU, MENGYAO SUN, QINHUAI LAI, YIN LU, YUYIN FU, YUJIA PENG, WEIRONG LAI, LISHI ZENG, SHENGYAN ZHAO, YUYAN LI, ZHIXIONG ZHANG, XIAOFENG CHEN, FAN QIAO, YIWEN ZHANG, SHIJIE ZHOU, LANTU GOU, JINLIANG YANG},
TITLE = {Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma},
JOURNAL = {BIOCELL},
VOLUME = {45},
YEAR = {2021},
NUMBER = {3},
PAGES = {589--597},
URL = {http://www.techscience.com/biocell/v45n3/41691},
ISSN = {1667-5746},
ABSTRACT = {The chemokine ligand 13-chemokine receptor 5 (<i>CXCL13-CXCR5</i>) 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 <i>CXCL13</i> in <i>kidney clear cell carcinoma</i> (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 <i>CXCL13</i> 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 <i>CXCL13</i> 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. <i>CXCL13</i> 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 <i>CXCL13</i> promoter hypomethylation was common in
TIICs. The methylation level of cg16361705 within the <i>CXCL13</i> promoter might play an important role in
modulating <i>CXCL13</i> transcription. In conclusion, our study revealed that <i>CXCL13</i> 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.},
DOI = {10.32604/biocell.2021.013882}
}