Therefore, it is most important for us to investigate effective targets for the treatment of liver metastasis. However, this research only focused on the development of diagnostic and prognostic markers without trying to identify gene signatures able to distinguish metastatic from primary cancer tissues ( 13). Comparative profiling of primary colon carcinomas and liver metastases identifies lymphoid enhancer factor-1 (LEF1) as a prognostic biomarker ( 13). The identified genes are specific to colon carcinoma and hepatic metastases, but the precise target is still unknown ( 12). Pairs of primary and metastatic tumors were analyzed and the samples clustered by patients but not the tissue origin ( 10, 11).
Such long lists of genes are difficult to be used for the development of new therapies ( 8, 9). Two studies presented gene signatures associated with metastatic disease containing more than 400 genes. Few attentions were focused on the gene signatures associated with metastatic disease ( 7). Gene expression profiling has become a strategy to identify genes involved in the progression and the prognosis of different cancers. Therefore, we attempt to investigate the malignant features of hepatic metastasis microenvironment by RNA-sequencing. Transcriptomic changes inherit from genomic information and take place before protein level. However, these have not revealed effective predicted factor which is specific to liver metastasis. Alterations in gene expression, protein expression, posttranslational modification, microRNA and linc-RNA have been reported to act a part of role in tumor progression. Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways inhibit metastasis to the liver ( 6). In addition, the CpG island methylator phenotype (CIMP) is concordant between primary colon carcinoma and distant metastases ( 5). MicroRNA 34a, microRNA-34a-5p, microRNA-340 are associated with colon carcinoma cell proliferation and metastasis ( 3, 4). There have been many attempts to determine predictive factors or explain the underlying mechanisms for distant metastasis. A major clinical challenge is to explore possible therapeutic targets that are specifically expressed in liver metastatic settings. However, most colon cancer patients with active metastasis appear to be resistant, or even non-responsive, to current treatments. In the majority of metastatic patients, the standard treatment remains palliative chemotherapy. Curative-intent resections can be performed in only 10%−15% of liver metastases ( 2). Unfortunately, about 70% of colon carcinoma patients develop liver metastases. Accepted for publication Oct 23, 2018.ĭoi: 10.21147/j.issn.1000-9604.2018.06.08Ĭolon carcinoma is one of the most common malignant diseases with 945,000 new cases every year and is the fourth cause of cancer-related deaths worldwide ( 1).
Gene set enrichment analysis (GSEA) showed that CXCL14 was negatively related to the regulation of stem cell proliferation and epithelial to mesenchymal transition (EMT).ĬXCL14 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.Ĭolon carcinoma liver metastasis mRNA profiling functions annotation Importantly, our validated data further suggested that lower CXCL14 represented poorer outcome and contributed to metastasis. 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. We identified 22 specific genes related to liver metastasis and they were strongly associated with cell migration, adhesion, proliferation and immune response. Then, the candidate genes were validated by our data. Survival analyses based on The Cancer Genome Atlas (TCGA) database were used to further screening. Co-expression network and protein-protein interaction (PPI) network were employed to identify the interaction relationship. Gene ontology (GO) and pathways of the identified genes were analyzed. 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. Thus, it is necessary to identify genes implicated in metastatic colonization of the liver in colon carcinoma.
Liver metastasis, which contributes substantially to high mortality, is the most common recurrent mode of colon carcinoma.
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