Ertao Zhai, Jianhui Chen, Kang Wang, Zhijun Ye, Hui Wu, Chuangqi Chen, Changjiang Qin, Sile Chen, Yulong He, Shirong Cai
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd road, Guangzhou, 510080, China.
Tumour Biol. 2016 Oct;37(10):13679-13685. doi: 10.1007/s13277-016-5229-1. Epub 2016 Jul 29.
The aim of this study was to detect mixed lineage kinase domain-like protein (MLKL) expression in gastric cancer (GC) and to analyze its association with the prognosis of GC patients. Immunohistochemical staining, Western blotting, and quantitative reverse-transcriptase polymerase chain reaction were performed to detect MLKL tissue expression in 117 GC patients. Clinicopathological characteristics and survival data were retrospectively analyzed to discover the clinical importance of MLKL expression. The chi-square test was used to analyze the relationship between MLKL expression and the clinicopathological characteristics. Survival curves were plotted by using the Kaplan-Meier method and compared using the log-rank test. Survival data were evaluated using univariate and multivariate Cox regression analyses. The expression of MLKL mRNA was significantly higher in adjacent normal samples than in the tumor tissues (P = 0.003). Clinicopathological analysis showed that MLKL expression was significantly correlated with age (P = 0.013), histologic type (P = 0.049), differentiation grade (P < 0.001), depth of invasion (P = 0.022), and lymph node metastasis (P = 0.003). Low MLKL expression was significantly associated with decreased overall survival (median 29 months vs. 56 months, P < 0.001). Multivariate analysis suggested that MLKL expression might be an independent prognostic indicator (HR = 0.645, 95 % CI, 0.446-1.165, P = 0.002) for GC patients. In conclusion, our findings provide evidence that MLKL might serve as a candidate tumor suppressor and a potential prognostic biomarker for GC.
本研究旨在检测胃癌(GC)中混合谱系激酶结构域样蛋白(MLKL)的表达,并分析其与GC患者预后的相关性。采用免疫组织化学染色、蛋白质印迹法及定量逆转录聚合酶链反应检测117例GC患者的MLKL组织表达。回顾性分析临床病理特征和生存数据,以发现MLKL表达的临床意义。采用卡方检验分析MLKL表达与临床病理特征之间的关系。用Kaplan-Meier法绘制生存曲线,并用对数秩检验进行比较。采用单因素和多因素Cox回归分析评估生存数据。MLKL mRNA在癌旁正常组织中的表达显著高于肿瘤组织(P = 0.003)。临床病理分析表明,MLKL表达与年龄(P = 0.013)、组织学类型(P = 0.049)、分化程度(P < 0.001)、浸润深度(P = 0.022)及淋巴结转移(P = 0.003)显著相关。低MLKL表达与总生存期降低显著相关(中位生存期29个月对56个月,P < 0.001)。多因素分析提示,MLKL表达可能是GC患者的独立预后指标(HR = 0.645,95%CI,0.446 - 1.165,P = 0.002)。总之,我们的研究结果表明,MLKL可能是一种候选肿瘤抑制因子,也是GC潜在的预后生物标志物。