Patients with high-grade serous ovarian carcinoma (HGSOC) gradually acquire resistance to standard chemotherapy after recurrence. In our previous study of HGSOC, histone deacetylase (HDAC)6 upregulation led to poor prognosis, and programmed cell death ligand-1(PD-L1) expressions positively correlated with HDAC6 expression. We analyzed the expression of HDAC6 and PD-L1 pre- and post-chemotherapy to investigate their association with chemotherapy resistance.
PD-L1 and HDAC6 expressions were immunohistochemically analyzed using clinical samples obtained before and after standard chemotherapy (combination of platinum and taxane agents) from 54 patients with HGSOC. The clinicopathological characteristics, including surgical status, RECIST status, and chemotherapy response score, were reviewed.
High expression (≥ 5%) of PD-L1 was detected in 5 and 8 cases pre- and post-chemotherapy, respectively. The mean PD-L1 positive rate post-chemotherapy was 3.88%, which was significantly higher than 0.68% pre- chemotherapy (p=0.045). The high expression frequency of HDAC6 significantly increased from 4 patients pre-chemotherapy to 13 patients post-chemotherapy (p=0.019). High PD-L1 expression post-chemotherapy was significantly correlated with chemotherapy response score 3, signifying chemosensitivity. High post-chemotherapy PD-L1 expression led to poor progression-free (p=0.037) and overall survival (p=0.049), in the group with complete surgical resection.
In HGSOC, residual tumors post-chemotherapy had enhanced expression of HDAC6 and PD-L1, which are associated with tumor immunity, cell proliferation, and hypoxic responses. PD-L1 was also correlated with patient prognosis. These results suggest that HDAC6 and PD-L1 may serve as therapeutic targets and prognostic factors for residual tumors after standard chemotherapy in HGSOC.