PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer.

Abstract

The heterogeneity of ovarian cancer (OC) has made developing effective treatments difficult. Nowadays, hormone therapy plays a growing role in the treatment of OC; however, hormone modulators have had only limited success so far. To provide a more rigorous foundation for hormonal therapy for different OC subtypes, the current study used a series of bioinformatics approaches to analyse the expression profiles of genes encoding membrane progesterone (PGRMC1, progestins and the adipoQ receptor [PAQR] family), and androgen (zinc transporter member 9 [ZIP9], OXER1) receptors. Our work investigated also their prognostic value in the context of OC. We found differences in expression of ZIP9 and OXER1 between different OC subtypes, as well as between patient tumour and normal tissues. Expression of mRNA encoding PAQR7 and PAQR8 in a panel of OC cell lines was below the qPCR detection limit and was downregulated in tumour tissue samples, whereas high expression of PGRMC1 and PAQR4 mRNA was observed in rare subtypes of OC cell lines. In addition, chemical inhibition of PGRMC1 reduced the viability of rare OCs represented by COV434 cells. In conclusion, PGRMC1 and PAQR4 are promising targets for anticancer therapy, particularly for rare subtypes of OC. These findings may reflect differences in the observed responses of various OC subtypes to hormone therapy.