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Biomarkers and Targets Identification among CXC Chemokines in the Colon Adenocarcinoma

Heng Wang, Changqing Guo, Jun Luo, Quan Li, Buqing Fubuqing*, Wei Jiang

Background: COAD is among the most prevalent malignancy, with a very high incidence rate. Crosstalk between cancer and interstitial cells significantly affects cancer development, modulated partly by chemokines production. When present in the tumor microenvironment, CXC chemokines have been shown to regulate tumor cell activity and influence immune cell transport, resulting in anti-tumor immune mechanisms and influencing the outcomes of the patient; nonetheless, the CXC chemokines expression levels in COAD, as well as their prognostic significance, have not yet been established.

Methods: This study used UALCAN, GeneMANIA, STRING, TRRUST, cBioPortal, TIMER, and GEPIA.

Results: The expression of CXC1/2/3/5/6/11/12/13/14/16/17 in COAD patients was shown to be significantly correlated with the pathological stage. A considerably improved prognosis was observed in patients with low transcriptional levels of CXCL9/10/11. Differentially expressed CXC chemokines exert roles that are predominantly correlated with the chemokine signaling pathway and interactions of cytokine–cytokine receptors. Our findings indicated that the transcriptional factors, including SP1, RELA, and NFKB1 are essential for the production of CXC chemokines. Furthermore, we discovered a substantial association between the CXC chemokines production and infiltration of 6 kinds of immune cells (CD8⁺ T cells, dendritic cells, B cells, CD4⁺ T cells, neutrophils, and macrophages,).

Conclusion: These findings might be useful in identifying prognostic indicators and immunotherapeutic targets for colon cancer.