Unravelling the link between embryogenesis and cancer metastasis

Kanisha Shah; Shanaya Patel; Sheefa Mirza; Rakesh M Rawal

doi:10.1016/j.gene.2017.11.056

Unravelling the link between embryogenesis and cancer metastasis

Gene. 2018 Feb 5:642:447-452. doi: 10.1016/j.gene.2017.11.056. Epub 2017 Nov 21.

Authors

Kanisha Shah¹, Shanaya Patel¹, Sheefa Mirza², Rakesh M Rawal³

Affiliations

¹ Division of Medicinal Chemistry & Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India.
² Division of Medicinal Chemistry & Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India; Department of Life Science, Gujarat University, Ahmedabad, Gujarat, India.
³ Department of Life Science, Gujarat University, Ahmedabad, Gujarat, India. Electronic address: rakeshrawal@gujaratuniversity.ac.in.

PMID: 29162510
DOI: 10.1016/j.gene.2017.11.056

Abstract

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, β-actin) were performed on 62 tissues (32 liver metastasis tissues and 30 primary Liver cancer tissues), Fetal liver tissues (below and above 20weeks 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 20weeks of gestation whereas it was up-regulated in fetal liver below 20weeks 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 20weeks of gestation but were not expressed during early embryo development (below 20weeks 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.

Keywords: Fetal liver; Gene profiling; Liver metastasis; Primary liver cancer; Real time PCR (qRT-PCR).

MeSH terms

Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18 / genetics
Data Curation
Data Mining
Embryonic Development*
Female
Gene Expression Profiling / methods*
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks*
Gestational Age
Humans
Liver / embryology*
Liver Neoplasms / genetics*
Liver Neoplasms / secondary
Matrix Metalloproteinase 9 / genetics
Osteopontin / genetics
Pregnancy
Protein Interaction Maps
Tumor Suppressor Protein p53 / genetics

Substances

CDKN2A protein, human
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18
SPP1 protein, human
TP53 protein, human
Tumor Suppressor Protein p53
Osteopontin
MMP9 protein, human
Matrix Metalloproteinase 9