The role of CXCL chemokine family in the development and prognosis of colorectal cancer

摘要

Objective:Colorectal cancer(CRC)is a major cause of cancer-related deaths worldwide.The class of chemokines known as cysteine-x-cysteine(CXC)motif ligands(CXCL)is thought to have a significant role in inflammation.A previous study implicated that CXCL family may play a role in angiogenesis and tumor development.In this comprehensive study,16 CXCLs in CRC will be analyzed for their prognostic values and expression patterns.Methods:To investigate CXCLs expression,immune cell infiltration,prognostic value significance,and genetic alteration among CRC patients,Gene Expression Profiling Interactive Analysis 2(GEPIA2),Kaplan-Meier plotter(K-M plotter),Gene Set Cancer Analysis(GSCA),STRING,GeneMANIA,and Sangerbox3.0 were employed.Results:As a result of our study,there was a significant increase in the levels of CXCL1/2/3/4/5/8/9/10/11/13/14/16 in CRC tissues,whereas CXCL12 was reduced.The expression of CXCL1/2/3/9/10/11 in CRC was linked to tumor stage.High expression of CXCL2/3/14 was associated with longer overall survival(OS)in colon adenocarcinoma(COAD)patients,and the overexpression of CXCL2/6/9/11/13 was related to long OS in rectum adenocarcinoma(READ)patients.Additionally,patients with CRC who expressed high levels of CXCL9/10/11 tended to have a longer disease-free survival(DFS).Furthermore,the functions of differentially expressed CXCLs were mainly involved in cytokine activity and chemokine effects.A significant correlation has been found between CXCLs expression and the infiltration of diverse immune cells in COAD and READ,including six types of CD4+T cells,macrophages,neutrophils,B cells,CD8+T cells,and dendritic cells.Conclusions:According to our study,CXCLs may not only serve as prognostic markers for CRC patients but also affect the immune status of CRC tissues,thereby providing new ideas for immunotherapy.