Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma
Abstract Patients with ovarian high-grade serous carcinoma (OHGSC) gradually acquire resistance to standard chemotherapy following recurrence. In our previous study on OHGSC, histone deacetylase (HDAC) 6 upregulation led to a poor prognosis, and programmed death ligand-1 (PD-L1) expression was posit...
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Nature Portfolio
2025-06-01
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| Online Access: | https://doi.org/10.1038/s41598-025-02329-9 |
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| author | Mitsutake Yano Tomomi Katoh Mariko Miyazawa Aiko Ogasawara Kosei Hasegawa Eiji Kobayashi Masanori Yasuda |
| author_facet | Mitsutake Yano Tomomi Katoh Mariko Miyazawa Aiko Ogasawara Kosei Hasegawa Eiji Kobayashi Masanori Yasuda |
| author_sort | Mitsutake Yano |
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| description | Abstract Patients with ovarian high-grade serous carcinoma (OHGSC) gradually acquire resistance to standard chemotherapy following recurrence. In our previous study on OHGSC, histone deacetylase (HDAC) 6 upregulation led to a poor prognosis, and programmed death ligand-1 (PD-L1) expression was positively correlated with HDAC6 expression. We analyzed HDAC6 and PD-L1 expression before and after chemotherapy to investigate their association with chemotherapy resistance and patient survival. PD-L1 and HDAC6 expression were immunohistochemically analyzed using clinical samples from 54 patients with OHGSC before and after standard chemotherapy. High PD-L1 expression (≥ 5%) was detected in five and nine patients before and after chemotherapy, respectively. The mean PD-L1-positive rate after chemotherapy was 3.88%, which was significantly higher than the rate before chemotherapy (0.68%). The high HDAC6 expression frequency significantly increased from four patients before chemotherapy to 13 patients after. High PD-L1 expression after chemotherapy was significantly correlated with a chemotherapy response score of three, signifying a good chemo-response. High PD-L1 expression after chemotherapy was associated with poor progression-free survival and overall survival in patients who underwent complete surgical resection. In OHGSC, residual tumors after chemotherapy show enhanced HDAC6 and PD-L1 expression. Upregulated PD-L1 after neoadjuvant chemotherapy (NAC) has contradictory characteristics, indicating a good response to chemotherapy but unfavorable survival. It is a wolf in sheep’s clothing, and physicians should not make an optimistic prognosis even if the patient shows a good response to NAC. HDAC6 and PD-L1 may be therapeutic targets and prognostic factors for residual tumors after chemotherapy in OHGSC. |
| format | Article |
| id | doaj-art-757eb2fde1824694a350d01e1af0e88e |
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| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-757eb2fde1824694a350d01e1af0e88e2025-08-20T02:05:40ZengNature PortfolioScientific Reports2045-23222025-06-011511810.1038/s41598-025-02329-9Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinomaMitsutake Yano0Tomomi Katoh1Mariko Miyazawa2Aiko Ogasawara3Kosei Hasegawa4Eiji Kobayashi5Masanori Yasuda6Department of Pathology, Saitama Medical University International Medical CenterDepartment of Pathology, Saitama Medical University International Medical CenterDepartment of Obstetrics and Gynaecology, Tokai University School of MedicineDepartment of Gynaecologic Oncology, Saitama Medical University International Medical CenterDepartment of Gynaecologic Oncology, Saitama Medical University International Medical CenterDepartment of Obstetrics and Gynaecology, Oita University Faculty of MedicineDepartment of Pathology, Saitama Medical University International Medical CenterAbstract Patients with ovarian high-grade serous carcinoma (OHGSC) gradually acquire resistance to standard chemotherapy following recurrence. In our previous study on OHGSC, histone deacetylase (HDAC) 6 upregulation led to a poor prognosis, and programmed death ligand-1 (PD-L1) expression was positively correlated with HDAC6 expression. We analyzed HDAC6 and PD-L1 expression before and after chemotherapy to investigate their association with chemotherapy resistance and patient survival. PD-L1 and HDAC6 expression were immunohistochemically analyzed using clinical samples from 54 patients with OHGSC before and after standard chemotherapy. High PD-L1 expression (≥ 5%) was detected in five and nine patients before and after chemotherapy, respectively. The mean PD-L1-positive rate after chemotherapy was 3.88%, which was significantly higher than the rate before chemotherapy (0.68%). The high HDAC6 expression frequency significantly increased from four patients before chemotherapy to 13 patients after. High PD-L1 expression after chemotherapy was significantly correlated with a chemotherapy response score of three, signifying a good chemo-response. High PD-L1 expression after chemotherapy was associated with poor progression-free survival and overall survival in patients who underwent complete surgical resection. In OHGSC, residual tumors after chemotherapy show enhanced HDAC6 and PD-L1 expression. Upregulated PD-L1 after neoadjuvant chemotherapy (NAC) has contradictory characteristics, indicating a good response to chemotherapy but unfavorable survival. It is a wolf in sheep’s clothing, and physicians should not make an optimistic prognosis even if the patient shows a good response to NAC. HDAC6 and PD-L1 may be therapeutic targets and prognostic factors for residual tumors after chemotherapy in OHGSC.https://doi.org/10.1038/s41598-025-02329-9Histone deacetylase 6Ovarian cancer: high-grade serous carcinomaProgrammed death ligand-1Prognosis, neoadjuvant chemotherapy |
| spellingShingle | Mitsutake Yano Tomomi Katoh Mariko Miyazawa Aiko Ogasawara Kosei Hasegawa Eiji Kobayashi Masanori Yasuda Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma Scientific Reports Histone deacetylase 6 Ovarian cancer: high-grade serous carcinoma Programmed death ligand-1 Prognosis, neoadjuvant chemotherapy |
| title | Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma |
| title_full | Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma |
| title_fullStr | Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma |
| title_full_unstemmed | Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma |
| title_short | Histone deacetylase 6 and programmed death ligand-1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high-grade serous carcinoma |
| title_sort | histone deacetylase 6 and programmed death ligand 1 expressions after neoadjuvant chemotherapy are upregulated in patients with ovarian high grade serous carcinoma |
| topic | Histone deacetylase 6 Ovarian cancer: high-grade serous carcinoma Programmed death ligand-1 Prognosis, neoadjuvant chemotherapy |
| url | https://doi.org/10.1038/s41598-025-02329-9 |
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