Comprehensive multiplatform biomarker analysis of 350 hepatocellular carcinomas identifies potential novel therapeutic options

Celina Ang, John T. Miura, T. Clark Gamblin, Ruth He, Joanne Xiu, Sherri Z. Millis, Zoran Gatalica, Sandeep K. Reddy, Nelson S. Yee, Ghassan K. Abou-Alfa

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background and Objectives Effective therapies for hepatocellular carcinoma (HCC) are limited. Molecular profiling of HCC was performed to identify novel therapeutic targets. Methods 350 HCC samples were evaluated using a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ), including gene sequencing, amplification, and protein expression. Results EGFR, TOPO1, PD-1, TOP2A, SPARC, and c-Met were overexpressed in 25-83% of samples. Decreased expression of RRM1,TS, PTEN, and MGMT occurred in 31-82% of samples. TP53 was mutated in 30%, CTNNB1 in 20%, and BRCA2 in 18%; other gene mutation rates were <5%. TP53-mutated tumors showed significantly higher TOPO2A (90% vs. 38%, P < 0.0001) and TS (56% vs. 29%, P = 0.0139) expression. CTNNB1-mutated tumors had significantly higher AR (56% vs. 21%, P = 0.0017), SPARC (61% vs. 29%, P = 0.0135), PDL1 (29% vs. 0%, P = 0.0256) expression, and BRCA2 mutations (50% vs. 6%, P = 0.0458). Metastases exhibited significantly higher infiltration by PD-1+ lymphocytes (79% vs. 50%, P = 0.047) and TS (31% vs. 14%, P < 0.0003) than primary HCC. Conclusions Multiplatform profiling reveals molecular heterogeneity in HCC and identifies potential therapies including tyrosine kinase, PI3 kinase, or PARP inhibitors for molecular subtypes. Chemotherapy may benefit some tumors. CTNNB1-mutated tumors may respond to multi-target inhibition. These limited and preliminary data require clinical validation.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalJournal of Surgical Oncology
Volume113
Issue number1
DOIs
StatePublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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    Ang, C., Miura, J. T., Clark Gamblin, T., He, R., Xiu, J., Millis, S. Z., Gatalica, Z., Reddy, S. K., Yee, N. S., & Abou-Alfa, G. K. (2016). Comprehensive multiplatform biomarker analysis of 350 hepatocellular carcinomas identifies potential novel therapeutic options. Journal of Surgical Oncology, 113(1), 55-61. https://doi.org/10.1002/jso.24086