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Chin J Cancer Res. 2018 Dec;30(6):633-646. doi: 10.21147/j.issn.1000-9604.2018.06.08.

Identification of liver metastasis-associated genes in human colon carcinoma by mRNA profiling.

Liu J1,2, Wang D1,2, Zhang C1,2, Zhang Z1,2, Chen X1,2, Lian J1,2, Liu J3, Wang G3, Yuan W3, Sun Z3, Wang W1,2, Song M1,2, Wang Y4, Wu Q1,2, Cao L1,2, Wang D1,2, Zhang Y1,2,5.

Author information

1
Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
2
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
3
Department of Anorectal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
4
Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou 450052, China.
5
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.

Abstract

Objective:

Liver metastasis, which contributes substantially to high mortality, is the most common recurrent mode of colon carcinoma. Thus, it is necessary to identify genes implicated in metastatic colonization of the liver in colon carcinoma.

Methods:

We compared mRNA profiling in 18 normal colon mucosa (N), 20 primary tumors (T) and 19 liver metastases (M) samples from the dataset GSE49355 and GSE62321 of Gene Expression Omnibus (GEO) database. Gene ontology (GO) and pathways of the identified genes were analyzed. Co-expression network and protein-protein interaction (PPI) network were employed to identify the interaction relationship. Survival analyses based on The Cancer Genome Atlas (TCGA) database were used to further screening. Then, the candidate genes were validated by our data.

Results:

We identified 22 specific genes related to liver metastasis and they were strongly associated with cell migration, adhesion, proliferation and immune response. Simultaneously, the results showed that C-X-C motif chemokine ligand 14 (CXCL14) might be a favorable prediction factor for survival of patients with colon carcinoma. Importantly, our validated data further suggested that lower CXCL14 represented poorer outcome and contributed to metastasis. Gene set enrichment analysis (GSEA) showed that CXCL14 was negatively related to the regulation of stem cell proliferation and epithelial to mesenchymal transition (EMT).

Conclusions:

CXCL14 was identified as a crucial anti-metastasis regulator of colon carcinoma for the first time, and might provide novel therapeutic strategies for colon carcinoma patients to improve prognosis and prevent metastasis.

KEYWORDS:

Colon carcinoma; functions annotation; liver metastasis; mRNA profiling

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