Lian Pei-Long, Liu Zhao, Yang Guang-Yun, Zhao Rui, Zhang Zhao-Yang, Chen Yue-Guang, Zhuang Zhuo-Nan, Xu Ke-Sen
Pei-Long Lian, Rui Zhao, Zhao-Yang Zhang, Yue-Guang Chen, Ke-Sen Xu, Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China.
World J Gastroenterol. 2016 Apr 14;22(14):3852-9. doi: 10.3748/wjg.v22.i14.3852.
To investigate the expression of integrin αvβ6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patients.
Immunohistochemistry was used to determine the expressions of integrin αvβ6 and MMP-9 in 126 specimens from patients with primary gastric carcinoma. Associations between immunohistochemical staining and various clinic pathologic variables of tissue specimens were evaluated by the χ(2) test and Fisher's exact test. Expression correlation of αvβ6 and MMP-9 was assessed using bivariate correlation analysis. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 56 mo (ranging from 2 mo to 94 mo). Four different combinations of αvβ6 and MMP-9 levels (that is, both markers positive, both markers negative, αvβ6 positive with MMP-9 negative, and αvβ6 negative with MMP-9 positive) were evaluated for their relative effect on survival. The difference in survival curves was evaluated with a log-rank test. Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis.
The expressions of integrin αvβ6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for αvβ6 expression, and 42.06% for MMP-9 expression. The expression of αvβ6 was associated with Lauren type, differentiation, N stage, and TNM stage (the P values were 0.006, 0.038, 0.016, and 0.002, respectively). While MMP-9 expression was associated with differentiation, T stage, N stage, and TNM stage (the P values were 0.039, 0.014, 0.033, and 0.008, respectively). The positive correlation between αvβ6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of αvβ6 or MMP-9 alone died earlier than those with negative expression and that patients who were both αvβ6 and MMP-9 positive had a shorter overall survival than those with the opposite pattern (both αvβ6 and MMP-9 negative) (P = 0.000). A Cox model indicated that positive expression of αvβ6 and MMP-9, diffuse Lauren type, as well as a senior grade of N stage, M stage, and TNM stage were predictors of a poor prognosis in univariate analysis. Only αvβ6 and MMP-9 retained their significance when adjustments were made for other known prognostic factors in multivariate analysis (RR = 2.632, P = 0.003 and RR = 1.813, P = 0.007).
The expression of αvβ6 and MMP-9 are closely correlated, and the combinational pattern of αvβ6 and MMP-9 can serve as a more effective prognostic index for gastric cancer patients.
研究整合素αvβ6和基质金属蛋白酶9（MMP-9）的表达、它们与预后因素的关系，并评估其在胃癌患者中的预测作用。
采用免疫组织化学法检测126例原发性胃癌患者标本中整合素αvβ6和MMP-9的表达。通过χ²检验和Fisher精确检验评估免疫组化染色与组织标本各种临床病理变量之间的关联。使用双变量相关分析评估αvβ6和MMP-9的表达相关性。患者在头两年每3个月随访一次，之后至少每6个月随访一次，中位随访时间为56个月（范围为2个月至94个月）。评估αvβ6和MMP-9水平的四种不同组合（即两种标志物均为阳性、两种标志物均为阴性、αvβ6阳性而MMP-9阴性、αvβ6阴性而MMP-9阳性）对生存的相对影响。用对数秩检验评估生存曲线的差异。采用Kaplan-Meier生存分析和Cox比例风险模型分析进行生存分析。
对126例患者检测整合素αvβ6和MMP-9的表达，其中αvβ6表达阳性率为34.92%，MMP-9表达阳性率为42.06%。αvβ6的表达与Lauren分型、分化程度、N分期和TNM分期相关（P值分别为0.006、0.038、0.016和0.002）。而MMP-9的表达与分化程度、T分期、N分期和TNM分期相关（P值分别为0.039、0.014、0.033和0.008）。相关性分析证实胃癌中αvβ6与MMP-9呈正相关。Kaplan-Meier生存分析显示，单独表达αvβ6或MMP-9的患者比表达阴性的患者死亡更早，且αvβ6和MMP-9均阳性的患者总生存期比相反模式（αvβ6和MMP-9均阴性）的患者短（P = 0.000）。Cox模型表明，在单因素分析中，αvβ6和MMP-9的阳性表达、弥漫性Lauren分型以及较高的N分期、M分期和TNM分期是预后不良的预测因素。在多因素分析中，对其他已知预后因素进行校正后，只有αvβ6和MMP-9仍具有统计学意义（RR = 2.632，P = 0.003；RR = 1.813，P = 0.007）。
αvβ6和MMP-9的表达密切相关，αvβ6和MMP-9的联合模式可作为胃癌患者更有效的预后指标。
