Comprehensive multiplatform biomarker analysis of 350 hepatocellular carcinomas identifies potential novel therapeutic options
Corresponding Author
Celina Ang MD
Department of Medicine, Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
Correspondence to: Celina Ang, MD, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1079, New York, NY 10029. Fax: +1-646 537 9639. E-mail: [email protected]
Search for more papers by this authorJohn T. Miura MD
Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
Search for more papers by this authorT. Clark Gamblin MD, MS
Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
Search for more papers by this authorRuth He MD, PhD
Department of Medicine, Hematology/Oncology, Georgetown University Medical Center, Washington, DC
Search for more papers by this authorSherri Z. Millis MS, PhD
Caris Life Sciences, Phoenix, Arizona
Sherri Z. Millis's current affiliation is Advanced Individual Medicine, LLC.Search for more papers by this authorNelson S. Yee MD, PhD
Department of Medicine, Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania
Search for more papers by this authorGhassan K. Abou-Alfa MD
Memorial Sloan Kettering Cancer Center, New York, New York
Department of Medicine, Hematology/Oncology, Weill Cornell Medical College, New York, New York
Search for more papers by this authorCorresponding Author
Celina Ang MD
Department of Medicine, Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
Correspondence to: Celina Ang, MD, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1079, New York, NY 10029. Fax: +1-646 537 9639. E-mail: [email protected]
Search for more papers by this authorJohn T. Miura MD
Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
Search for more papers by this authorT. Clark Gamblin MD, MS
Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
Search for more papers by this authorRuth He MD, PhD
Department of Medicine, Hematology/Oncology, Georgetown University Medical Center, Washington, DC
Search for more papers by this authorSherri Z. Millis MS, PhD
Caris Life Sciences, Phoenix, Arizona
Sherri Z. Millis's current affiliation is Advanced Individual Medicine, LLC.Search for more papers by this authorNelson S. Yee MD, PhD
Department of Medicine, Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania
Search for more papers by this authorGhassan K. Abou-Alfa MD
Memorial Sloan Kettering Cancer Center, New York, New York
Department of Medicine, Hematology/Oncology, Weill Cornell Medical College, New York, New York
Search for more papers by this authorAbstract
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.
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