Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma
Background Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001679.full |
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| author | Akimichi Morita Hiroshi Kato Motoki Nakamura Kotaro Nagase Maki Yoshimitsu Tetsuya Magara Yuka Nojiri Tadahiro Kobayashi Yukiko Teramoto Masahito Yasuda Hidefumi Wada Toshiyuki Ozawa Yukie Umemori Dai Ogata |
| author_facet | Akimichi Morita Hiroshi Kato Motoki Nakamura Kotaro Nagase Maki Yoshimitsu Tetsuya Magara Yuka Nojiri Tadahiro Kobayashi Yukiko Teramoto Masahito Yasuda Hidefumi Wada Toshiyuki Ozawa Yukie Umemori Dai Ogata |
| author_sort | Akimichi Morita |
| collection | DOAJ |
| description | Background Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes. We performed RNA sequencing to evaluate the immune response and comprehensively estimate prognostic values of immunogenic factors in patients with MCC.Methods We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC at 10 facilities. The mRNA was extracted from formalin-fixed paraffin-embedded tissues. Next-generation sequencing, immunohistochemical staining and blood serum tests were performed.Results Next-generation sequencing results classified MCC samples into two types: the ‘immune active type’ was associated with better clinical outcomes than the ‘cell division type’. Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene was highly significantly upregulated in the ‘cell division type’. Among 395 genes, G6PD expression correlated with the presence of lymph node or distant metastases during the disease course and significantly negatively correlated with PD-L1 expression. Immunohistochemical staining of G6PD also correlated with disease-specific survival and exhibited less heterogeneity compared with PD-L1 expression. G6PD activity could be measured by a blood serum test. The detection values significantly increased as the cancer stage progressed and significantly decreased after treatment.Conclusions G6PD expression was an immunohistochemically and serum-detectable prognostic marker that negatively correlated with immune activity and PD-L1 levels, and could be used to predict the immunotherapy response. |
| format | Article |
| id | doaj-art-2f5725b1c69c4446b64afea2feedf8dc |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-2f5725b1c69c4446b64afea2feedf8dc2024-11-09T23:15:12ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001679Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinomaAkimichi Morita0Hiroshi Kato1Motoki Nakamura2Kotaro Nagase3Maki Yoshimitsu4Tetsuya Magara5Yuka Nojiri6Tadahiro Kobayashi7Yukiko Teramoto8Masahito Yasuda9Hidefumi Wada10Toshiyuki Ozawa11Yukie Umemori12Dai Ogata133 Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, JapanDepartment of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan2 Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan1 Departments of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan1 Departments of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan3 Department of Molecular Pathology of Skin, Faculty of Medicine, Kanazawa University, Kanazawa, Japan4 Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Hidaka, Japan5 Department of Dermatology, Gunma University, Maebashi, Japan6 Environmental Immuno-Dermatology, Yokohama City University, Yokohama, Japan7 Department of Dermatology, Osaka City University, Osaka, Japan8 Division of Dermatology, Nagaoka Red Cross Hospital, Nagaoka, Japan9 Department of Dermatology, Saitama Medical University, Iruma-gun, JapanBackground Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes. We performed RNA sequencing to evaluate the immune response and comprehensively estimate prognostic values of immunogenic factors in patients with MCC.Methods We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC at 10 facilities. The mRNA was extracted from formalin-fixed paraffin-embedded tissues. Next-generation sequencing, immunohistochemical staining and blood serum tests were performed.Results Next-generation sequencing results classified MCC samples into two types: the ‘immune active type’ was associated with better clinical outcomes than the ‘cell division type’. Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene was highly significantly upregulated in the ‘cell division type’. Among 395 genes, G6PD expression correlated with the presence of lymph node or distant metastases during the disease course and significantly negatively correlated with PD-L1 expression. Immunohistochemical staining of G6PD also correlated with disease-specific survival and exhibited less heterogeneity compared with PD-L1 expression. G6PD activity could be measured by a blood serum test. The detection values significantly increased as the cancer stage progressed and significantly decreased after treatment.Conclusions G6PD expression was an immunohistochemically and serum-detectable prognostic marker that negatively correlated with immune activity and PD-L1 levels, and could be used to predict the immunotherapy response.https://jitc.bmj.com/content/8/2/e001679.full |
| spellingShingle | Akimichi Morita Hiroshi Kato Motoki Nakamura Kotaro Nagase Maki Yoshimitsu Tetsuya Magara Yuka Nojiri Tadahiro Kobayashi Yukiko Teramoto Masahito Yasuda Hidefumi Wada Toshiyuki Ozawa Yukie Umemori Dai Ogata Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma Journal for ImmunoTherapy of Cancer |
| title | Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma |
| title_full | Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma |
| title_fullStr | Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma |
| title_full_unstemmed | Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma |
| title_short | Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma |
| title_sort | glucose 6 phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand 1 expression in merkel cell carcinoma |
| url | https://jitc.bmj.com/content/8/2/e001679.full |
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