Comprehensive analysis of CXCL14 uncovers its role during liver metastasis in colon cancer

Background: The most common cause of death for colon cancer patients is liver metastasis.

Methods: All the data enrolled in this study were downloaded from two public databases, The Cancer Genome Atlas Program, the TCGA-COAD project and Gene Expression Omnibus, GSE41258 project. All the analysis was performed in R software.

Results: In our study, we systematically explored the molecules involved in the liver metastasis process of colon cancer. The biological role of these molecules was identified through the GO and KEGG analysis. Moreover, we identified that the molecules SERPINA3, SERPINA1, MMP3, ALDH1A3, PBK and CXCL14 were the independent factors for patients survival. The CXCL14 was selected for further analysis for its most significant P value. Single-cell analysis showed that the CXCL14 was mainly expressed in the fibroblasts. Meanwhile, the biological role of fibroblasts in the colon cancer microenvironment was investigated. Further, the clinical role of CXCL14 in colon cancer was also explored. The result showed that the CXCL14 is a protective factor against colon cancer independent of other clinical parameters like age, gender, clinical stage, and TNM classifications. Then, biological enrichment analysis indicated that the CXCL14 is predominantly involved in the activating of the WNT/β/catenin pathway, pancreas beta cells, peroxisome and bile acid metabolism. Immune infiltration analysis showed that for the patients with high CXCL14 levels, the plasma B cells, CD8 + T cells, neutrophil and NK cells might infiltrate more, in contrast to B cells, monocyte and macrophages. Furthermore, we found that the patients with low CXCL14 expression might be more sensitive to etoposide, rapamycin and sunitinib.

Conclusions: Our result could improve the understanding of the liver metastasis process in colon cancer. Also, CXCL14 was identified as an underlying therapeutic target for colon cancer.