PBOV1 correlates with progression of ovarian cancer and inhibits proliferation of ovarian cancer cells

Abstract

Prostate and breast cancer overexpressed 1 (PBOV1) is significantly upregulated in prostate, breast and bladder cancer, while its expression status in ovarian cancer and its clinical significance are unclear. We examined the expression levels of PBOV1 mRNA and protein in ovarian cancer cell lines and primary tissues using real-time PCR and western blotting. Immunohistochemistry was employed to analyze PBOV1 expression in 17 normal ovaries, 13 cystadenoma tissues, 14 borderline tumor tissues, and 165 clinicopathologically characterized ovarian cancers. There was negative PBOV1 expression in the 17 normal ovarian epithelial tissues. Compared to the normal ovarian epithelial cells, PBOV1 mRNA and protein were overexpressed in ovarian cancer cell lines. There was high PBOV1 protein expression in the ovarian cancer tissues from 59 of the 165 (35.8%) patients; PBOV1 expression was weak in 106 (64.2%) patients. Notably, there were significant negative associations between high PBOV1 expression and ascending histological grade, late pT/pN/pM, and International Federation of Gynecology and Obstetrics (FIGO) stage (P<0.05). Patients with high PBOV1 expression had longer overall survival; patients with low PBOV1 expression had shorter survival. Multivariate analysis revealed that PBOV1 upregulation is an independent prognostic indicator for ovarian cancer and might serve as a tumor-suppressor gene. Furthermore, PBOV1 overexpression inhibited ovarian cancer cell proliferation and tumorigenesis in vitro and in a tumor transplantation nude mouse model. In conclusion, our results suggest that PBOV1 may play an important role in suppressing ovarian cancer proliferation and carcinogenesis. PBOV1 may be a novel and useful prognostic marker and potential target for treating human ovarian cancer.

PBOV1 as a potential biomarker for more advanced prostate cancer based on protein and digital histomorphometric analysis

“…A possible role for PBOV1 as an immune-modulating protein that enhances survival outcomes in ovarian cancers has been proposed based on its higher mRNA and protein expression in early stage tumors (stage I-II) compared to higher staged tumors (III-IV). 16 Our results in PCa samples from radical prostatectomy failed to reveal high protein levels in lower grade tumors. However, outcome data on our patient groups were unavailable, and thus we could not determine whether PBOV1 protein expression levels impact overall or long-term survival.…”

“…A possible role for PBOV1 as an immune‐modulating protein that enhances survival outcomes in ovarian cancers has been proposed based on its higher mRNA and protein expression in early stage tumors (stage I–II) compared to higher staged tumors (III–IV) . Our results in PCa samples from radical prostatectomy failed to reveal high protein levels in lower grade tumors.…”

“…These results suggested possible “immunoediting” of PBOV1‐expressing tumor cells, whereby PBOV1 serves as a tumor antigen facilitating immune attack and elimination of tumor cells based on the presence of PBOV1. A more recent study demonstrated that high levels of PBOV1 mRNA and protein levels in ovarian cancer correlate positively with longer survival and negatively with ascending histological grade, also consistent with a possible immune‐stimulatory role for PBOV1 in this setting. Further studies found that PBOV1 transcription is positively correlated with androgen concentration and is downregulated with increasing estradiol doses, suggesting that gene expression is hormone‐dependent…”

“…Proteins were extracted using previously described methods. 20 The PBOV1 antibody used in this study was validated as previously described 12 and recognizes epitope B of the PBOV1 protein (amino acids [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Beta actin (1:15,000, Sigma-Aldrich, St. Louis, MO) was used as a control for data normalization.…”

Association between the overexpression of PBOV1 and the prognosis of patients with hepatocellular carcinoma

“…It was also identified that the expression of PBOV1 in prostate cancer cells is upregulated by dihydrotestosterone (12). In addition, PBOV1 transcription in breast cancer cells was demonstrated to be downregulated by estradiol in a dose-dependent manner (13), and the mRNA and protein expression of PBOV1 was identified to be upregulated in ovarian cancer cell lines (14). However, there were negative associations between high PBOV1 expression and ascending histological grade and late TNM stage (14).…”