title: Prognostic and clinicopathological significance of Cacna2d1 expression in epithelial ovarian cancers: a retrospective study.
abstract: Ovarian cancer is the most lethal gynecologic malignancy, in which cancer stem cells (CSC) have been reported to be the driving force of relapse and therapy-resistance. It is therefore important to explore CSC markers in ovarian cancer. This project aimed to explore the correlation between the expression of potential CSC maker Cacna2d1 and clinicopathological parameters in 238 epithelial ovarian cancer (EOC) samples. Immunohistochemically, positive Cacna2d1 expression was observed in 83.6% (199/238) of the EOC tumors, among which 107 tumors (44.9%) were highly positive and 92 (38.7%) tumors were weakly positive for the Cacna2d1 protein expression. Among the 158 serous carcinomas, the Cacna2d1 positivity was 148 (93.7%), in which 88 (55.7%) were highly positive, and 60 (38.0%) were weakly positive for the Cacna2d1 protein expression. Most strikingly, the Cacna2d1 was specifically expressed in the infiltration front areas of the EOC tumors. Statistical analyses showed that positive expression of Cacna2d1 was significantly associated with advanced FIGO stage (P<0.001), histological subtype (P=0.017) and tumor differentiation (P=0.015). Positive Cacna2d1 protein expression was significantly associated with poor overall survival (OS) and shorter progression free survival (PFS) in both total EOCs and serous carcinomas, although multivariate analyses did not reach statistical significance. In summary, our results suggest Cacna2d1 protein may play a crucial role in promoting aggressive EOC behavior and progression, and Cacna2d1 may serve as a novel predictive prognostic marker and a potential target for therapeutic intervention in EOCs.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityHenan, China; Department of Pathology, The Norwegian Radium Hospital, Oslo University HospitalOslo 0424, Norway.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital Oslo 0424, Norway.
authors.forename: Ruth
authors.initials: R
authors.lastname: Holm
authors.affiliation: Department of Surgery, The Norwegian Radium Hospital, Oslo University Hospital Oslo 0424, Norway.
authors.forename: Mariusz Adam
authors.initials: MA
authors.lastname: Goscinski
authors.affiliation: Department of Gynaecology, The Norwegian Radium Hospital, Oslo University HospitalOslo 0424, Norway; Department of Gynaecology, Institute of Clinical Medicine, Faculty of Medicine, University of OsloOslo 0379, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University HospitalOslo 0424, Norway; Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of OsloOslo 0379, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityHenan, China; Department of Pathology, The Norwegian Radium Hospital, Oslo University HospitalOslo 0424, Norway; Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of OsloOslo 0379, Norway.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
keywords: Cacna2d1; Ovarian carcinoma; cancer stem cell; immunohistochemistry; molecular pathology