RESUMO
PURPOSE: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study is to identify differentially expressed proteins (DEPs) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP) and analyze their relationships to cellular mechanisms involved in the pathogenesis of POP. EXPERIMENTAL DESIGN: Uterosacral ligament connective tissue from four patients with POP and four control women undergo iTRAQ analysis followed by ingenuity pathway analysis (IPA) of DEPs. DEPs are validated using Western blot analysis. RESULTS: A total of 1789 unique protein sequences are identified in the uterosacral ligament connective tissues. The expression levels of 88 proteins are significantly different between prolapse and control groups (≥1.2-fold, p < 0.05). IPA demonstrates the association of 14 DEPs with "Connective Tissue Function." Among them, fibromodulin, collagen alpha-1 (XIV) chain, calponin-1, tenascin, and galectin-1 appear most likely to play a role in the etiology of POP. CONCLUSIONS AND CLINICAL RELEVANCE: At least six proteins not previously associated with the pathogenesis of POP with biologic functions that suggest a plausible relationship to the disorder are identified. These results may be helpful for furthering the understanding of the pathophysiological mechanisms of POP.
Assuntos
Regulação da Expressão Gênica , Ligamentos/metabolismo , Prolapso de Órgão Pélvico/metabolismo , Proteoma/biossíntese , Proteômica , Adulto , Feminino , Humanos , Ligamentos/patologia , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/patologiaRESUMO
OBJECTIVE: To explore the clinicopathologic factors associated with prognosis in patients with rectal cancer. METHODS: Clinicopathologic data of 2414 patients with rectal cancer, treated in the Affiliated Tumor Hospital of Harbin Medical University from May 1976 to December 2003, were analyzed retrospectively. Cox regression model was used to assess independent factors associated with prognosis. RESULTS: The median survival time was 58 months and the 5-year overall survival rate was 45.1%. Tumors were stage I( in 75.2%, stage II( in 48.1%, stage III( in 21.3%, and stage â £( in 8.8% of the patients. The 5-year overall survival rates during the three study periods were 41.2%(1976-1986), 43.0%(1987-1996), and 49.1%(1997-2003)(P<0.01). On univariate analysis, age, time at diagnosis, histological type, distant metastasis, type of surgery, intent of surgery, gross morphology, pathologic T stage, lymphatic invasion, bowel obstruction, and TNM stage showed statistically significant association with survival. Independent prognostic factors on multivariable analysis were gross tumor morphology chi-squared value(CV):68.744, pT(CV:81.344), lymphatic invasion(CV:42.951), bowel obstruction(CV:37.856) and TNM stage(CV:85.329). CONCLUSIONS: Survival in patients with rectal cancer is improved over time. TNM stage is the most important prognostic factor for survival in patients with rectal cancer.