A discovery of anti-tumor immunity-related biomarkers for Merkel cell carcinoma using next-generation sequencers.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Nagoya City University
• Principal Investigator: Nakamura Motoki 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70645051)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: メルケル細胞癌 / バイオマーカー / 免疫チェックポイント阻害薬

Outline of Final Research Achievements

We collected 90 specimens from 71 patients (26 men, median age 77.3 years) with MCC from 9 facilities. Next-generation sequencing of mRNA from 40 FFPE MCC samples revealed that glucose-6-phosphate dehydrogenase (G6PD) correlated with PD-L1 expression and metastasis. Kaplan-Meier survival analysis revealed a poor prognosis for patients with high-G6PD expression. G6PD+ immunostaining predicted MCC patient prognosis, with a median survival of 3.4 years for G6PD+ patients and 6.7 years for G6PD- patients. G6PD activity assay was performed using 50 serum samples from 19 cases. Three cases showed high G6PD activity, and two of them were all of stage Ⅳ cases and the last one was stage Ⅱ and died of another cause soon after sampling. G6PD regulates NADPH production and high G6PD expression enhances cellular oxidative resistance. G6PD is a promising marker to stratify MCC patients into high- and low-risk groups.
These results were reported as J Immunother Cancer. 2020 Dec;8(2):e001679.

Free Research Field

皮膚癌

Academic Significance and Societal Importance of the Research Achievements

進行期メルケル細胞癌の治療には免疫チェックポイント阻害薬が使用されることが多いが、約半数の患者が治療抵抗性であり、適切な治療選択、効果予測のためにバイオマーカーの発見が急務であった。今回発見した抗腫瘍免疫の活性に基づくバイオマーカーである、グルコース-6-リン酸脱水素酵素により、免疫チェックポイント阻害薬の効果の予測、モニタリングが可能となり、より適切な治療選択が可能になると考える。