Gsα蛋白与腹膜假黏液瘤临床病理特征及预后的相关性研究

  目的  探讨鸟苷酸结合蛋白α亚基（guanine nucleotide binding protein alpha subunit，Gsα）表达与腹膜假黏液瘤（pseudomyxoma peritonei，PMP）主要临床病理特征及预后的相关性。  方法  收集首都医科大学附属北京世纪坛医院65例PMP患者病理标本，行常规组织病理学和定量免疫组织化学检测Gsα蛋白表达，研究Gsα蛋白表达与主要临床病理特征及预后的相关性。  结果  65例PMP肿瘤行定量免疫组织化学分析，Gsα高表达者35例（53.8%），低表达者30例（46.2%）。单因素分析显示，Gsα高表达与下列5个临床病理指标呈正相关:术前肿瘤标志物（χ2=3.68，P=0.087）、术中腹水量（χ2=3.69，P=0.055）、腹膜癌指数评分（peritoneal cancer index，PCI）（χ2=3.12，P=0.077）、肿瘤细胞减灭程度评分（completeness of cytoreduction，CC）（χ2=2.72，P=0.099）、组织病理分级（χ2= 5.85，P=0.016）。多因素分析显示，Gsα蛋白高表达仅与组织病理分级呈独立正相关:高级别或高级别伴印戒细胞的组织病理类型（OR=3.47，95%CI:1.1 ～ 15.6，P=0.029）。Cox多因素分析显示，年龄（HR=8.08，95%CI:2.42 ～ 26.97，P=0.001）、既往手术（HR=0.24，95%CI:0.07 ～ 0.81，P=0.022）、组织病理分级（HR=3.92，95%CI:1.12 ～ 13.70，P=0.032）；Gsα蛋白表达（HR=3.25，95%CI:1.01 ～ 10.5，P=0.048）为独立预后因素。  结论  Gsα蛋白高表达与高级别或高级别伴印戒细胞的组织病理类型呈正相关，提示PMP预后不良。 

Correlation between Gsα protein expression and clinicopathological characteristics and prognosis of pseudomyxoma peritonei

  Objective  To explore the correlation between the expression of guanine nucleotide binding protein alpha subunit (Gsα) and the main clinicopathological characteristics and prognosis of pseudomyxoma peritonei (PMP).   Methods  Sixty-five postoperative specimens from PMP patients following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were collected. Routine histopathological examination was performed and quantitative immunohistochemical analysis was conducted to evaluate Gsα protein expression. Univariate and multivariate analyses were performed to explore the correlations between the Gsα protein expression levels and the major clinicopathological characteristics—including survival status—of patients.   Results  Among the 65 PMP patients, 35 (53.8%) showed a high expression whereas 30 (46.2%) showed a low expression of the Gsα protein. Clinicopathological factors positively correlated with a high expression of Gsα in univariate analysis included increased preoperative tumor marker levels (χ2=3.68, P=0.087), intraoperative ascite volume (χ2=3.69, P=0.055), peritoneal cancer index (PCI) score (χ2=3.12, P=0.077), completeness of cytoreduction (CC) score (χ2=2.72, P=0.099), and histopathological grade (χ2=5.85, P=0.016). Multivariate analysis confirmed a high-grade disease with/ without signet ring cells as the only independent pathological factor positively correlated with a high expression of Gsα odds ratio (OR)=3.47, P=0.029]. Cox regression analysis identified four independent prognostic factors: age hazard ratio (HR)=8.08, 95% confidence interval (CI): 2.42-26.97, P=0.001], presence of past surgery (HR=0.24, 95%CI: 0.07- 0.81, P=0.022), histopathological grade (HR=3.92, 95%CI: 1.12-13.70, P=0.032), and Gsα protein expression (HR=3.25, 95%CI: 1.01-10.5, P=0.048).   Conclusions  High expression of the Gsα protein is positively correlated with high-grade PMP with/ without signet ring cells, and is indicative of poor prognosis.