MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular
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ORIGINAL ARTICLE – CANCER RESEARCH
MET canonical transcript expression is a predictive biomarker for chemo‑sensitivity to MET‑inhibitors in hepatocellular carcinoma cell lines Wafaa M. Rashed1 · Mohamed A. Kandeil2 · Mohamed O. Mahmoud3 · Doha Maher4 · Sameera Ezzat5 · Mohamed H. Abdel Rahman4,6,7 Received: 5 May 2020 / Accepted: 16 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 METinhibitors 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. Keywords MET gene · L1-MET transcript · MET protein · Hepatocellular carcinoma · Crizotinib · Tivantinib
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03395-4) contains supplementary material, which is available to authorized users. * Mohamed H. Abdel Rahman Mohamed.Abdel‑[email protected] 1
Worldwide, hepatocellular carcinoma (HCC) ranks as the fifth most common cancer and represents the most lethal cancer (Ferlay et al. 2015; Siegel et al. 2016). Currently, 5
Department of Epidemiology and Prevention Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
Department of Research, Children’s Cancer Hospital, Egypt, Cairo, Egypt
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Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef, Egypt
Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
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Departmen
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