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Comprehensive multiplatform biomarker analysis of 350 hepatocellular carcinomas identifies potential novel therapeutic options
Author(s) -
Ang Celina,
Miura John T.,
Gamblin T. Clark,
He Ruth,
Xiu Joanne,
Millis Sherri Z.,
Gatalica Zoran,
Reddy Sandeep K.,
Yee Nelson S.,
AbouAlfa Ghassan K.
Publication year - 2016
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.24086
Subject(s) - pten , medicine , hepatocellular carcinoma , cancer research , gene expression profiling , targeted therapy , gene , oncology , gene expression , cancer , biology , pi3k/akt/mtor pathway , apoptosis , biochemistry
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. J. Surg. Oncol. 2016;113:55–61 . © 2015 Wiley Periodicals, Inc.