title: Decreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma.
abstract: Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, but the expression status in epithelial ovarian tumors has not been investigated. In this study, immunohistochemistry for PinX1 protein was performed on a tissue microarray (TMA) of epithelial ovarian tumors (informatively containing 25 cystadenomas, 29 borderline tumors, and 157 invasive carcinomas) and 12 normal ovaries. Receiver-operator curve (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patients' survival status. The threshold for PinX1 positivity was determined to be above 60% (area under the curve = 0.856, P < 0.001) based on the area under the ROC. Positive expression of PinX1 was observed in 100% of normal ovarian tissues, in 84% of cystadenomas, in 75.9% borderline tumors, and 66.2% of ovarian carcinomas. Decreased expression of PinX1 was strongly related to patients with poor prognostic factors regarding presence of lymph node metastasis (P = 0.024), distant metastasis (P < 0.001), and late International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001). In univariate survival analysis, a highly significant correlation between loss of PinX1 and shortened patient survival (mean, 48.2 months vs 99.2 months, P < 0.001) was displayed. Multivariate analysis demonstrated PinX1 expression (P = 0.027) was evaluated as an independent parameter. Our findings suggest that loss of PinX1 is an adverse independent molecular marker for epithelial ovarian carcinoma patients. PinX1 may be a novel target for telomerase-based anticancer therapy due to inhibiting telomerase activity.
authors.affiliation: Sun Yat-Sen University, Guangzhou, China.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: He
authors.forename: Guo-Fen
authors.initials: GF
authors.lastname: Yang
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Rao
authors.forename: Zhi-Yue
authors.initials: ZY
authors.lastname: Rao
authors.forename: Qiu-Liang
authors.initials: QL
authors.lastname: Wu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D019098:Telomerase / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C440808:PINX1 protein, human; D025521:Tumor Suppressor Proteins; C509186:TERT protein, human; D019098:Telomerase