C chemokines are prognostic biomarkers correlated with diverse immune cell infiltrations in clear cell renal cell carcinoma

Abstract

Background: The interplay between tumor-infiltrating immune cells and cancer cells affects cancer initiation, progression, and treatment. C chemokines are critically involved in immune cell chemotaxis, selftolerance formation, antigen cross-presentation, and cytotoxic immune response. However, their roles in cancer development are still largely unknown.Methods: We comprehensively analyzed the expression, prognostic value, functions, and immune implication of C chemokines in clear cell renal cell carcinoma (ccRCC) using multiple databases. Besides, we detected the expression of C chemokines in RCC cell lines using quantitative real-time polymerase chain reaction (qPCR).Results: Through analyzing The Cancer Genome Atlas (TCGA), Oncomine and Gene Expression Omnibus (GEO) ccRCC datasets, we found that C chemokines were significantly upregulated in ccRCC tumor tissues and associated with tumor progression. Besides, qPCR revealed the overexpression of C chemokines in RCC cell lines. Promoter hypomethylation was a potential factor causing the upregulation of C chemokines. ccRCC patients with higher levels of C chemokines had significantly poorer overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). C chemokines and related genes were involved mainly in cytokine-cytokine receptor interactions and the chemokine signaling and Toll-like receptor signaling pathways. Correlation analysis revealed a positive correlation between C chemokines and the infiltration of 25 immune cell subtypes, many of which affected the prognosis of ccRCC. Moreover, C chemokines were positively correlated with the expression of genes associated with M2 macrophage polarization and T-cell exhaustion, and the expression of several immune checkpoints in ccRCC.Conclusions: Our research provides preliminary insights into the prognostic value and immune implication of C chemokines in ccRCC, which is conducive to the prediction of survival and immunotherapy response, and the development of novel therapeutic targets for ccRCC.

PPP1R14B is a diagnostic prognostic marker in patients with uterine corpus endometrial carcinoma

“…The results showed that PPP1R14B expression was negatively correlated with eosinophils, iDCs, mast cells, neutrophils, and other immune cells. Immune cell infiltration can improve the poor prognosis of patients, and low concentrations of infiltrating immune cells can lead to immune escape of cancer cells, resulting in poor prognosis 58,59 . In addition, the results of immune infiltration showed that the degree of Th2 cell infiltration was significantly positively correlated with the expression of PPP1R14B.…”

“…Immune cell infiltration can improve the poor prognosis of patients, and low concentrations of infiltrating immune cells can lead to immune escape of cancer cells, resulting in poor prognosis. 58,59 In addition, the results of immune infiltration showed that the degree of Th2 cell infiltration was significantly positively correlated with the expression of PPP1R14B. The transition from Th1/Th2 balance to Th2 dominance is a crucial factor in tumour progression, and Th2 cells are not conducive to the antitumour effect of cellular immunity.…”

NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis

“…The correlation between NUDT21 expression and 24 types of immune cells in PAAD showed that NUDT21 expression was negatively correlated with NK cells, pDC, and Th17 cells. Immune cell infiltration improves poor patient prognosis, whereas low concentrations of infiltrating immune cells can lead to immune escape from cancer cells, resulting in poor prognosis (Buisseret et al 2018 ; Chen et al 2020 ). In addition, the results of immune infiltration showed that the degree of Th2 cell infiltration was significantly positively correlated with the expression of NUDT21.…”

A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma

“…Thus, CXCL13 up-regulation has been shown to correlate with advanced disease stage and poor prognosis ( 71 ). In addition, XCL1 positively correlated with the expression of several inhibitory receptors and cytokines that are associated with T cell exhaustion and several immune checkpoints in ccRCC, thus resulting in a significantly poorer survival ( 72 ). However, as evident from a comparison of concordance indexes of the multi-parameter model consisting of solely clinical and demographic variables and the model including gene expression parameters, there was no add-on value of the investigated chemokine gene expression levels to the prediction accuracy of OS or response to immunotherapy.…”