Shusuke Yoshikawa1, Yoshio Kiyohara1, Masaki Otsuka1, Ryota Kondou2, Chizu Nonomura2, Haruo Miyata2, Akira Iizuka2, Keiichi Ohshima3, Kenichi Urakami4, Takeshi Nagashima5, Masatoshi Kusuhara6, Takashi Sugino7, Tohru Mochizuki3, Ken Yamaguchi8, Yasuto Akiyama9. 1. Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka, Japan. 2. Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 3. Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 4. Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 5. SRL Inc., Tokyo, Japan. 6. Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 7. Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan. 8. Office of the President, Shizuoka Cancer Center Hospital, Shizuoka, Japan. 9. Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan y.akiyama@scchr.jp.
Abstract
BACKGROUND: Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade. MATERIALS AND METHODS: The patients with melanoma comprised of six males and seven females, and their mean age was 68 years. Five patients were treated with nivolumab, and two were responders. RESULTS: GEP analysis demonstrated that PD-L1 expression was positive in for cases, and melanoma-associated antigens and tumor signaling-associated genes were up-regulated in tumor compared with normal tissues. Additionally, WES analysis indicated more single nucleotide variants (SNVs) per melanoma tumor compared to other tumor types. Remarkably, a case of complete remission after nivolumab therapy showed high expression of PD-L1 protein and the highest number of SNVs. CONCLUSION: The novel approach used in Project HOPE might be an efficient tool that facilitates identifying specific biomarkers predictive of good responders to anti-PD-1 therapy. Copyright
BACKGROUND: Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade. MATERIALS AND METHODS: The patients with melanoma comprised of six males and seven females, and their mean age was 68 years. Five patients were treated with nivolumab, and two were responders. RESULTS: GEP analysis demonstrated that PD-L1 expression was positive in for cases, and melanoma-associated antigens and tumor signaling-associated genes were up-regulated in tumor compared with normal tissues. Additionally, WES analysis indicated more single nucleotide variants (SNVs) per melanoma tumor compared to other tumor types. Remarkably, a case of complete remission after nivolumab therapy showed high expression of PD-L1 protein and the highest number of SNVs. CONCLUSION: The novel approach used in Project HOPE might be an efficient tool that facilitates identifying specific biomarkers predictive of good responders to anti-PD-1 therapy. Copyright