Upregulation of Abelson interactor protein 1 predicts tumor progression and poor outcome in epithelial ovarian cancer

Hum Pathol. 2015 Sep;46(9):1331-40. doi: 10.1016/j.humpath.2015.05.015. Epub 2015 May 30.

Abstract

Abelson interactor protein 1 (Abi1) is a key regulator of actin reorganization and lamellipodia formation. Because of its role in cell migration, Abi1 has been implicated in tumor progression. In the present study, we investigated the role of Abi1 in epithelial ovarian cancer (EOC) by analyzing its expression and correlation with clinicopathological and survival data. We evaluated the expression of Abi1 in 223 paraffin-embedded EOC specimens by immunohistochemistry and 46 frozen EOC samples by Western blot and real-time reverse transcription polymerase chain reaction analysis. Results showed that Abi1 protein and mRNA expression was significantly higher in EOC tissue compared with noncancerous tumors and normal ovaries (P < .05). Moreover, high level of Abi1 expression was significantly correlated with advanced stage, high grade, elevated Ca-125 level, and suboptimal surgical debulking (P < .05). By Western blot analysis, Abi1 was expressed in highly invasive cells compared with weakly invasive cells (P < .05). Immunofluorescence was performed to demonstrate Abi1 expression in SKOV3 cells. Additionally, upregulation of Abi1 significantly correlated with shorter survival (P < .05). Most importantly, multivariate analysis showed that Abi1 overexpression is an independent prognostic factor, complementary to clinical stage and residual tumor size. In conclusion, our findings suggest that Abi1 acts as a tumor-promoting gene in EOC progression, which may lead to unfavorable prognosis. Abi1 may serve as a potential effective prognostic marker for EOC.

Keywords: Abelson interactor protein 1; Invasion; Ovarian cancer; Prognosis; Progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Tumor Burden
  • Up-Regulation
  • Young Adult

Substances

  • ABI1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Cytoskeletal Proteins
  • RNA, Messenger