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Journal of Cancer Research and Clinical Oncology

Erschienen in:

26.09.2020 | Original Article – Cancer Research

MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular carcinoma cell lines

verfasst von: Wafaa M. Rashed, Mohamed A. Kandeil, Mohamed O. Mahmoud, Doha Maher, Sameera Ezzat, Mohamed H. Abdel-Rahman

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2021

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Abstract

Purpose

Long interspersed nuclear element 1 (LINE-1 or L1) is a dominant non-long terminal repeat (non-LTR) retrotransposon in the human genome that has been implicated in the overexpression of MET. Both the canonical MET and L1-MET transcripts are considered to play a role in hepatocellular carcinoma (HCC) development. The aim of this study was to assess the utility of canonical MET, L1-MET, and MET protein expressions as predictive biomarkers for chemo-sensitivity to MET-inhibitors in HCC cell lines in vitro. Additionally, we assessed their expression in tumour tissues from Egyptian HCC patients.

Methods

MET and L1-MET expressions were assessed by qRT-PCR in six liver cancer cell lines (SNU-387, SNU-475, SK-HEP-1, PLC/PRF/5, SNU-449 and SNU-423) and 47 HCC tumour tissues. MET protein expression was measured by western blot in cell lines and immunohistochemistry in the tumours. Cell proliferation assay was used to assess the effect of crizotinib and tivantinib on the six liver cancer cell lines in correlation with the expression of MET, L1-MET and MET.

Results

The antitumor effect of crizotinib and tivantinib correlated with MET gene expression but not with L1-MET transcript or MET protein expressions. No significant difference was observed between HCC tumours and non-tumour samples in MET and L1-MET transcripts expression. There were no significant correlations between the 2-year overall survival rate and the MET, L1-MET transcripts and the MET protein expression.

Conclusion

MET RNA expression could be useful biomarker for tivantinib and crizotinib targeted therapy in HCC. The value of assessment of MET protein expression is limited.

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Titel: MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular carcinoma cell lines
verfasst von: Wafaa M. Rashed
Mohamed A. Kandeil
Mohamed O. Mahmoud
Doha Maher
Sameera Ezzat
Mohamed H. Abdel-Rahman
Publikationsdatum: 26.09.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03395-4

Springer Medizin

MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular carcinoma cell lines