Ji Kun, Zhang Liyan, Zhang Mingxuan, Chu Qi, Li Xin, Wang Wei
From the Department of Pathophysiology, Shenyang Medical College, Shenyang (KJ, LZ); Grade 2012 Clinical Medicine, Shenyang Medical College, Shenyang (MZ, QC); Department of Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun (XL); and Department of Neurosurgery, The Second Clinical Medical School of Inner Mongolia University for the Nationalities (Inner Mongolia General Forestry Hospital), Inner Mongolia, China (WW).
Medicine (Baltimore). 2016 Feb;95(5):e2641. doi: 10.1097/MD.0000000000002641.
The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28-4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan-Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma.
在多种人类肿瘤中均检测到磷酸化信号转导子与转录激活子3(p-stat3)的过表达。关于胃癌患者中p-stat3表达的已发表研究仍存在争议。为了阐明p-stat3对胃癌患者总生存期的预后价值及其与临床病理特征的关联,我们进行了一项系统评价和荟萃分析。通过检索PubMed、Embase、Cochrane图书馆和中国生物医学文献服务系统数据库来获取符合条件的研究。这些研究描述了p-stat3表达与胃癌患者临床病理特征及总生存期之间的关联;p-stat3表达通过免疫组织化学(IHC)检测。比值比(OR)和风险比(HR)被视为荟萃分析中评估关联的指标;I用于评估各研究间的异质性;采用漏斗图、Egger检验和Begg检验评估发表偏倚。纳入了23项研究,共2872例患者,这些研究通过IHC评估了胃癌中p-stat3的表达。汇总的HR(HR = 2.02,95%CI:1.49 - 2.73,P < 0.00001)表明p-stat3表达增加与总生存期差显著相关。此外,当我们研究p-stat3过表达与胃癌临床病理特征之间的关联时,发现p-stat3表达增加与肿瘤分化(低分化vs中高分化:OR = 3.70,95%CI:1.98 - 6.93,P < 0.0001)和淋巴结转移(有vs无:OR = 2.40,95%CI:1.28 - 4.50,P = 0.007)显著相关。使用了不同类型的一抗;对p-stat3阳性表达的评估方法定义不同;p-stat3表达的位置不同;从Kaplan-Meier生存曲线推断HR的方法似乎不如直接从文献中提取HR可靠;样本量、患者年龄和随访时间各不相同。总之,我们的荟萃分析表明,p-stat3表达增加不仅可能预示预后不良,还与胃癌患者更差的肿瘤分化和淋巴结转移相关。