Fig. 7

PLD2 overexpression is associated with resistance to treatment in ovarian cancer. (A) Representative images of PLD2 immunostaining in ovarian cancer and non-tumoral samples. Scale bars, 200 μm. (B) PLD2 expression in ovarian patients from the HUVR-IBIS database. Box plots showing the PLD2 expression levels in ovarian tumor tissue (black) or nontumor tissue (red) from patients. Box plots representing the centre line, median; box limits, 25th and 75th percentiles; whiskers, minimum and maximum values. (C-D) Analysis of PLD2 expression by RT‒qPCR in a cohort of (C) OC patients or (D) only HGSOC patients who were sensitive (S; pink) or resistant (R; green) to platinum treatment (HUVR-IBIS). For B and C, the mRNA expression was calculated as 2^−∆Ct relative to the ACTB gene. (E-F) Kaplan‒Meier plots showing overall or progression-free survival in patients who were sensitive (pink) or resistant (green) to platinum treatment in the HUVR-IBIS cohort. (G-H) Determination of the IC₅₀ of cis-platinum and carboplatin in ES-2, SKOV3 and OVCAR8 cells overexpressing PLD2 or shPLD2 or carrying EV in (G) normoxia and hypoxia, (H) in combination or without the PLD inhibitor (PLDi) FIPI in ES-2, SKOV3 and OVCAR8 cells overexpressing shPLD2 or PLD2 or carrying EV in normoxia or hypoxia. (I-J) Determination of the tumor volume (I) and survival (J) after treatment with saline (-), cisplatin (Cis-Pt), the PLD inhibitor FIPI (PLDi) or both (Cis-Pt + PLDi) in xenografts of SKOV3 or OVCAR8 cells expressing PLD2 or EV. A minimum of three biological were performed per each experiment. The data were compared using Student’s t tests. *p < 0.05; **p < 0.01; ***p < 0.001