title: Comparative proteomic analysis of advanced serous epithelial ovarian carcinoma: possible predictors of chemoresistant disease.
abstract: To identify specific proteins associated with chemotherapeutic responses, we analyzed protein expression patterns in stage IIIc primary serous epithelial ovarian cancer tissues displaying differential responses to first-line postoperative adjuvant chemotherapy. The expression profiles of five chemoresistant tissues [progression-free survival (PFS) ≤12 months] and five chemosensitive tissues (PFS ≥48 months) were analyzed with 2D electrophoresis, and the spot intensities of differentially expressed proteins were quantified. To validate these proteins as markers for chemoresistant disease, we analyzed tissues from an additional 17 patients. All the patients were allocated to the over- or underexpressing group according to protein spot intensity, and survival analysis was performed. In chemoresistant tissues, four proteins (thioredoxin domain containing four, similar to RIKEN cDNA 1700016G05, tubulin α 1A chain, and the pyruvate dehydrogenase E1-β subunit precursor) were overexpressed, and seven proteins [keratin 1, vitamin D-binding protein, creatine kinase B, annexin V, SH3-containing guanine nucleotide exchange factor (SGEF), tryptophan-aspartate repeat protein-1 (WDR 1), and WDR 1 isoform 1] were underexpressed. The underexpression of keratin 1, creatine kinase B, annexin V, SGEF, WDR1, and WDR1 isoform 1 were significantly correlated with poor overall survival. A combination of keratin 1 and SGEF showed the highest sensitivity of 0.800, specificity of 0.917, PPV of 0.800, and NPV of 0.917 in predicting chemoresistant disease. These proteins may be useful as predictive markers of chemoresistant disease. However, further analyses in large-scale should be performed before they can be considered reliable predictive markers of chemoresistant disease.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Wun
authors.initials: SW
authors.lastname: Kim
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Nam
authors.forename: Yong Wook
authors.initials: YW
authors.lastname: Jeong
authors.forename: San Hui
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji Heum
authors.initials: JH
authors.lastname: Paek
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
mesh_terms: D000328:Adult; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D040901:Proteomics; D012372:ROC Curve; D016019:Survival Analysis