ARID1A mutation/ARID1A loss is associated with a high immunogenic profile in clear cell ovarian cancer
| Autor: | Kensuke Sakai, Wataru Yamagami, Mio Takahashi, Tatsuyuki Chiyoda, Miho Kawaida, Tomoko Yoshihama, Kohei Nakamura, Keiko Saotome, Eriko Aimono, Naomi Iwasa, Hiroshi Nishihara, Daisuke Aoki, Takuma Yoshimura, Yuka Kuroda |
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| Rok vydání: | 2021 |
| Předmět: |
endocrine system diseases
ARID1A medicine.medical_treatment Carcinoma Ovarian Epithelial PD-L1 Biomarkers Tumor Humans Medicine Ovarian Neoplasms biology business.industry Obstetrics and Gynecology Immunotherapy medicine.disease Immune checkpoint Cystadenocarcinoma Serous DNA-Binding Proteins Gene Expression Regulation Neoplastic Oncology Mutation Cancer research biology.protein Immunohistochemistry Biomarker (medicine) Female Neoplasms Cystic Mucinous and Serous business Ovarian cancer Clear cell Transcription Factors |
| Zdroj: | Gynecologic Oncology. 162:679-685 |
| ISSN: | 0090-8258 |
| Popis: | ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer.We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases.ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p0.001) or CD8 levels (p0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p0.001) and HGSC (p0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006).ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC. |
| Databáze: | OpenAIRE |
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