Proteomic landscaping of high‐grade serous ovarian carcinoma identifies stearoyl‐CoA desaturase 5 as a potential predictive biomarker for poly(ADP‐ribose) polymerase inhibitor response

To gain more functional insight, we performed gene set enrichment analysis and found that ribosomal and infection-related proteins were upregulated in the good response group, while ECM-receptor proteins and coagulation-related proteins were upregulated in the poor response group (Figure 2C and Figure S5). The M16 and platinum-free interval (PFI) had a negative correlation, consistent with literature that links a short PFI to an unfavourable response to PARPi.3 Remarkably, the protein-protein interaction map showed that the top-ranked three proteins from the feature selection were closely associated with the M16 (Figure 4B). In HGSOC, PARPi resistance mechanisms involve drug efflux, alterations in PAR metabolism, mutational and epigenetic changes, protection of replication fork with stability, and restoration of the homologous recombination pathway.7–9 Notably, deficiency of SCD5 in OVKATE and OVCAR3 cells affected the expression of several genes associated with PARPi resistance, including DNA repair and the Switch/Sucrose non-fermenting chromatin remodelling complex (Figure S9), increasing cell sensitivity to PARPi depending on double-strand DNA repair mechanisms. [...]the Kaplan-Meier plot showed that high SCD5 expression was significantly associated with worse PFS in HGSOC patients who received platinum-based chemotherapy10 (Figure S10). ETHICS STATEMENT This study was approved by the Institutional Review Board of Seoul National University Hospital (No.