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Multi-omics Profiling of Patients with Melanoma Treated with Nivolumab in Project HOPE
Shusuke Yoshikawa1, Yoshio Kiyohara1, Masaki Otsuka1
1Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
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.
Insights
Project HOPE identified biomarkers for cancer immunotherapy. Multi-omics analysis of melanoma patients revealed specific genetic markers associated with positive responses to programmed cell death-1 (PD-1) blockade therapy.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Project HOPE (High-tech Omics-based Patient Evaluation) initiated in 2014.
- Utilizes whole-exome sequencing (WES) and gene expression profiling (GEP).
- Focuses on multi-omics analysis for cancer biomarker discovery.
Purpose of the Study:
- Investigate specific biomarkers in melanoma patients responding to programmed cell death-1 (PD-1) blockade.
- Evaluate the utility of multi-omics data in predicting treatment response.
- Identify predictive biomarkers for anti-PD-1 therapy.
Main Methods:
- Multi-omics analyses including WES and GEP on 13 melanoma patients.
- Characterization of patients treated with nivolumab.
- Comparison of gene expression and mutational profiles between responders and non-responders.
Main Results:
- Positive PD-L1 expression observed in some cases.
- Upregulation of melanoma-associated antigens and tumor signaling genes in tumors.
- Melanoma tumors exhibited higher single nucleotide variant (SNV) counts compared to other tumor types.
- A complete remission case showed high PD-L1 expression and the highest SNV count.
Conclusions:
- Project HOPE's novel approach may efficiently identify biomarkers for anti-PD-1 therapy responders.
- Multi-omics profiling can aid in predicting patient response to immunotherapy.
- High SNV load and PD-L1 expression may correlate with favorable responses to PD-1 blockade.