Comprehensive analysis of the prognosis and immune infiltration for CXC chemokines in colorectal cancer

Abstract

The C-X-C motif (CXC) chemokines are a family of chemotactic molecules that have been identified as potential prognostic markers and prospective therapeutic targets for many kinds of cancer types. Increasing evidence shows that CXC chemokines are associated with the progression of colorectal cancer (CRC); however, the correlations of CXC chemokines with prognostic and immune infiltrates in CRC remain to be clarified. In this study, we analyzed the mRNA expression level, prognostic data and immune infiltrates of CXC chemokines in CRC patients from the Gene Expression Profiling Interactive Analysis, Oncomine, cBioPortal and databases using GeneMANIA, STRING, DAVID 6.8, and TIMER. Our results showed that CXCL1/2/3/4/5/8/9/10/11/13/14/16 were significantly overexpressed in CRC tissues. Furthermore, expression of CXCL1/2/3/9/10/11 was associated with tumor stage in CRC. A significant association was also identified between the co-expression of CXCL16 with EGFR, KRAS and NRAS. In addition, the survival analysis suggested that high CXCL2/3/8/9/10/11/14 expression is correlated with clinical outcomes of CRC patients. Moreover, a significant association was observed between the CXCL8/9/10/11 expression and immune infiltration in colonic and rectal adenocarcinoma. Overall, CXC chemokines are not only implicated as prognostic biomarkers for CRC patients, but may also influence the immune status of CRC tissues.

Keywords: CXC chemokines; colorectal cancer; comprehensive analysis; immune infiltration.

Figure 1

The mRNA expression levels of CXC chemokines in different types of cancers (Oncomine). The figure presents the numbers of datasets with statistically significant mRNA over-expression (red) or downregulated expression (blue) of CXC chemokines.

Figure 2

The mRNA expression pattern of CXC chemokines (CXCL1/2/3/4/5/6/7/8/9/10/11/12/13/14/16/17) from GEPIA between CRC tissues (red) and normal tissues (blue). The P-value was set at 0.05, ^* indicate that the results are statistically significant.

Figure 3

The prognostic value of different expressed CXC chemokines in CRC patients in OS (GEPIA). The OS curve of CXCL2/3/8/14 in (A) COAD + READ and (B) COAD.

Figure 4

The prognostic value of different expressed CXC chemokines in CRC patients in DFS (GEPIA). The DFS curve of CXCL9/10/11 in (A) COAD + READ and (B) COAD.

Figure 5

The expression protein of CXCL2/3/8/9/10/11/14 in CRC tissues and noncancerous tissues (IHC).

Figure 6

CXC chemokines gene expression and mutation analysis in CRC (cBioPortal). (A) Summary of alterations in CXC chemokines (cBioPortal). (B) OncoPrint visual summary of alteration on a query of CXC chemokines (cBioPortal). (C) Correction between different CXC chemokines in CRC (cBioPortal). (D) Gene-gene interaction network (GeneMANIA) and protein-protein interaction network (STRING) among CXC chemokines.

Figure 7

The association between the CXC chemokines expression and immune infiltration level of multiple immune cells types estimated by all six algorithms in ad heatmap table across COAD and READ. The red indicates a statistically significant positive association (P ≤ 0.05, rho > 0), and the blue indicates a statistically significant negative association (P ≤ 0.05, rho < 0). White denotes a non-significant result (P > 0.05).

Figure 8

The association between the CXC chemokines expression and immune markers in ad heatmap table across COAD and READ. The red indicates a statistically significant positive association (P ≤ 0.05, rho > 0), and the blue indicates a statistically significant negative association (P ≤ 0.05, rho < 0). White denotes a non-significant result (P > 0.05).