Liu Qilong, Li Wenfeng, Yang Shibin, Liu Zhaoguo
Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510089, Guangdong, China.
Department of General Thoracic Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510089, Guangdong, China,
Onco Targets Ther. 2018 Nov 29;11:8427-8434. doi: 10.2147/OTT.S181701. eCollection 2018.
The aim of the study was to investigate the relationship between urokinase-type plasminogen activator (uPA) and mitogen-activated protein kinase 38 (p38MAPK), and preliminarily analyze their relationship with clinical characteristics of esophageal cancer.
Immunohistochemistry and Western blot were used to detect the expressions of uPA and p38MAPK in patients with esophageal cancer. The relationship between them and clinicopathological features was analyzed by chi-squared test and Spearman correlation. Prognosis was performed using Kaplan-Meier and Cox proportional hazard models analysis.
The expressions of uPA and p38MAPK proteins were significantly higher in esophageal squamous cell carcinoma or adenocarcinoma than in normal esophageal mucosa tissue (both <0.0001). The expression of uPA was significantly correlated with the depth of invasion of esophageal cancer (=0.0067), tumor size (=0.0364), and pathological stage (<0.0001); p38MAPK expression vs esophageal cancer tissue type (=0.0043), esophageal cancer infiltration depth (=0.0097), tumor size (=0.0015), and pathological stage (<0.0001). Both were not significantly associated with lymph node staging, gender, age, and esophageal cancer histological type. There was a positive correlation between uPA and p38MAPK expressions (=0.7301, =0.0104). Kaplan-Meier analysis showed that the overall survival time of patients with positive expression of uPA or p38MAPK protein was significantly shorter, and the time of recurrence or metastasis of esophageal cancer was significantly earlier in patients with uPA-positive expression. Multivariate analysis of Cox model showed that uPA, p38MAPK, and pathological staging were independent factors influencing survival.
The expressions of uPA and p38MAPK may play an important role in the progression of esophageal cancer, and there is a close relationship between the two proteins, which may be one of the prognostic indicators.
本研究旨在探讨尿激酶型纤溶酶原激活剂(uPA)与丝裂原活化蛋白激酶38(p38MAPK)之间的关系,并初步分析它们与食管癌临床特征的关系。
采用免疫组织化学和蛋白质印迹法检测食管癌患者中uPA和p38MAPK的表达。通过卡方检验和Spearman相关性分析它们与临床病理特征之间的关系。采用Kaplan-Meier法和Cox比例风险模型分析预后。
食管鳞状细胞癌或腺癌中uPA和p38MAPK蛋白的表达明显高于正常食管黏膜组织(均<0.0001)。uPA的表达与食管癌的浸润深度(=0.0067)、肿瘤大小(=0.0364)和病理分期(<0.0001)显著相关;p38MAPK表达与食管癌组织类型(=0.0043)、食管癌浸润深度(=0.0097)、肿瘤大小(=0.0015)和病理分期(<0.0001)相关。两者均与淋巴结分期、性别、年龄和食管癌组织学类型无显著关联。uPA和p38MAPK表达之间存在正相关(=0.7301,=0.0104)。Kaplan-Meier分析显示,uPA或p38MAPK蛋白阳性表达患者总生存时间明显缩短,uPA阳性表达患者食管癌复发或转移时间明显提前。Cox模型多因素分析显示,uPA、p38MAPK和病理分期是影响生存的独立因素。
uPA和p38MAPK的表达可能在食管癌进展中起重要作用,且两种蛋白之间关系密切,可能是预后指标之一。