Unravelling the link between embryogenesis and cancer metastasis

Purpose: Cancer as opposed to embryonic development is characterized by dysregulated, uncontrolled and clonal growth of cells. Inspite of that they share certain commonality in gene expression patterns and a number of cellular & molecular features. Consequently, in the present study we aimed to evaluate the role of a definite set of genes in fetal liver, primary liver cancers and metastatic liver tissue. Methods: The relative expression of fourteen candidate genes obtained by data mining and manual curation of published data (CXCL12, CXCR4, CK7, CDH1, CTNNB1, CLDN4, VEGFA, HIF1A, MMP9, p53, OPN, CDKN2A, TGFBR2, MUC16, beta-actin) were performed on 62 tissues (32 liver metastasis tissues and 30 primary Liver cancer tissues), Fetal liver tissues (below and above 20 weeks of gestation) and 2 sets of control samples by real-time quantitative reverse transcription PCR (qRT-PCR). Results: Results showed significant down-regulation of MMP9 and TP53 in Fetal liver above 20 weeks of gestation whereas it was up-regulated in fetal liver below 20 weeks of gestation, primary liver cancers and liver metastasis. Contradictory to that OPN and CDKN2A were significantly up-regulated in primary liver cancer, liver metastasis; down-regulated in fetal liver above 20 weeks of gestation but were not expressed during early embryo development (below 20 weeks of gestation). Moreover, MMP9 and TP53 demonstrated a strong correlation with MUC16 whereas CDKN2A and OPN showed correlation with CXCL12/CXCR4 signifying that MUC16, CXCL12/CXCR4 might be involved in the complex process of cancer metastasis. Conclusion: MMP9, OPN, TP53 and CDKN2A were the identified markers that were expressed in a similar pattern in early embryonic development and cancer development & invasion suggesting that these genes are activated during embryogenesis and might be re-expressed in cancer metastasis. Moreover, these genes govern a pathway that might be activated during cancer metastasis. Thus, targeting these molecules may provide better treatment for metastatic liver cancers.