Yano Mitsutake, Katoh Tomomi, Miyazawa Mariko, Ogasawara Aiko, Hasegawa Kosei, Kobayashi Eiji, Yasuda Masanori
Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan.
Department of Obstetrics and Gynaecology, Oita University Faculty of Medicine, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan.
Sci Rep. 2025 Jun 2;15(1):19231. doi: 10.1038/s41598-025-02329-9.
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.
卵巢高级别浆液性癌（OHGSC）患者复发后会逐渐对标准化疗产生耐药性。在我们之前关于OHGSC的研究中，组蛋白去乙酰化酶（HDAC）6上调导致预后不良，且程序性死亡配体-1（PD-L1）表达与HDAC6表达呈正相关。我们分析了化疗前后HDAC6和PD-L1的表达，以研究它们与化疗耐药性及患者生存的关系。使用54例OHGSC患者标准化疗前后的临床样本，对PD-L1和HDAC6表达进行免疫组织化学分析。化疗前和化疗后分别有5例和9例患者检测到高PD-L1表达（≥5%）。化疗后PD-L1阳性率平均为3.88%，显著高于化疗前（0.68%）。HDAC6高表达频率从化疗前的4例显著增加至化疗后的13例。化疗后高PD-L1表达与化疗反应评分为3显著相关，表明化疗反应良好。化疗后高PD-L1表达与接受完全手术切除患者的无进展生存期和总生存期较差相关。在OHGSC中，化疗后的残留肿瘤显示HDAC6和PD-L1表达增强。新辅助化疗（NAC）后上调的PD-L1具有矛盾的特征，表明对化疗反应良好但生存期不佳。它是披着羊皮的狼，即使患者对NAC反应良好，医生也不应做出乐观的预后判断。HDAC6和PD-L1可能是OHGSC化疗后残留肿瘤的治疗靶点和预后因素。
