术前血清ITGβ6水平对CEA正常的可切除胃癌患者预后的预测价值

Prognostic value of preoperative serum ITGβ6 level in resectable gastric cancer patients with normal CEA

目的 探讨术前血清整合素β6(ITGβ6)水平对癌胚抗原(CEA)正常的可切除胃癌患者预后的预测价值。方法 收集2015年1月至2017年5月间在我院普外科接受手术的295例胃癌患者的病历资料,术前CEA≤5 ng/ml。另外收集同时期150例健康志愿者作为对照组。术前和术后30 d(辅助化疗前)收集患者血清标本。随机选取胃癌患者和对照组各6份血清样本(胃癌患者术前血清样本),采用液相色谱-质谱法(LC-MS/MS)进行血清蛋白组学分析。采用酶联免疫吸附测定法检测所有血清样本ITGβ6水平。Kaplan-Meier法绘制总生存期(OS)和无病生存期(DFS)曲线。采用Cox风险比例回归模型分析影响患者DFS和OS的因素。结果 经LC-MS/MS血清蛋白组学分析,存在71个差异性表达蛋白,其中ITGβ6上调最明显。与对照组比较,胃癌组患者血清ITGβ6基线水平升高[4.16(1.70,9.48) ng/ml vs. 0.32(0.09,1.03) ng/ml,P<0.001]。与术前比较,术后胃癌患者血清ITGβ6水平降低[1.14(0.20,2.42) ng/ml vs. 4.16(1.70,9.48) ng/ml,P<0.001]。p N分期、肿瘤直径、分化程度、血清CA199水平、血清CA242水平与血清ITGβ6基线水平有关(P<0.05)。血清ITGβ6高水平组(>4.16 ng/ml)患者OS和PFS较低水平组(≤4.16 ng/ml)更差(P<0.05)。多因素Cox风险比例模型结果显示,血清ITGβ6基线水平>4.16 ng/ml与较短的PFS和OS有关(P<0.05)。结论 术前血清ITGβ6水平对CEA水平正常的胃癌患者预后有良好的预测价值。

Objective To investigate the prognostic value of preoperative serum integrinβ6(ITGβ6)level in resectable gastric cancer patients with normal carcinoembryonic antigen(CEA).Methods The medical records of 295 patients with gastric cancer who underwent surgery in our hospital from January 2015 to May 2017 were collected.Preoperative CEA was lower than 5 ng/ml.Another 150 healthy volunteers were included as control group.Serum samples were collected before and 30 days after surgery(before adjuvant chemotherapy).Six serum samples were randomly selected from patients with gastric cancer and six from the control group(preoperative serum samples from patients with gastric cancer).Liquid chromatography-mass spectrometry(LC-MS/MS)was used for serum proteomic analysis.ITGβ6 levels in all serum samples were detected by enzyme-linked immunosorbent assay.Overall survival(OS)and disease-free survival(DFS)were plotted by Kaplan-Meier method.Cox proportional hazard regression model was used to analyze the influencing factors of DFS and OS.Results By LC-MS/MS serum proteomic analysis,71 differentially expressed proteins were found,among which ITGβ6 was the most up-regulated.Compared with the control group,the baseline level of serum ITGβ6 in gastric cancer group was increased[4.16(1.70,9.48)ng/ml vs.0.32(0.09,1.03)ng/ml,P<0.001].Compared with preoperative ITGβ6 level,serum ITGβ6 level in gastric cancer patients decreased[1.14(0.20,2.42)ng/ml vs.4.16(1.70,9.48)ng/ml,P<0.001].pN stage,tumor diameter,differentiation degree,serum CA199 level and serum CA242 level were correlated with the baseline serum ITGβ6 level(P<0.05).Patients with high ITGβ6 level(>4.16 ng/ml)had worse OS and PFS than those with low ITGβ6 level(≤4.16 ng/ml)(P<0.05).Multivariate Cox proportional hazard model showed that baseline serum ITGβ6 level>4.16 ng/ml was associated with shorter PFS and OS(P<0.05).Conclusion Preoperative serum ITGβ6 level has a good prognostic value for gastric cancer patients with normal CEA level.