S100钙结合蛋白 A2在胃癌组织中的表达及意义

摘要

目的：探讨 S100A2在慢性胃炎、肠上皮化生和胃癌组织样本中的表达及与胃癌临床病理特征及预后的关系。方法：利用 HE 染色对所取胃组织标本进行病理组织学诊断；采用免疫组织化学方法检测标本S100A2蛋白的表达；qRT - PCR 法检测 S100A2 mRNA 表达；Western blot 检测 S100A2蛋白的表达；采用 Kap-lan - Meier 分析累积生存率。结果：应用 qRT - PCR 方法分析不同胃组织标本 S100A2 mRNA 的表达水平，发现 S100A2 mRNA 的表达水平按以下顺序递减：胃炎，肠上皮化生，胃癌（ P ＜0.001），与 Western bolt 分析S100A2蛋白的表达评定结果相吻合。免疫组化分析：S100A2在胃炎、肠上皮化生和胃癌组织细胞质中表达， S100A2阳性表达率为胃炎100％（73/73），肠上皮化生90.7％（78/86），胃癌48.9％（170/348）（P ＜0.001）。在胃癌中，S100A2蛋白的表达缺失在青年患者中多于老年患者。S100A2蛋白的表达与肿瘤大小、浸润深度、淋巴管和静脉浸润、淋巴结转移、肿瘤 TNM 分期呈负相关，并随胃癌分化程度降低，在高分化癌、中分化癌和低分化癌中，S100A2的阳性表达率分别为65.9％、56.4％和17.2％（P ＜0.05），和患者性别无相关性（ P ＞0.05）。Kaplan - Meier 分析累积生存率显示：弱或中度 S100A2基因表达的患者累积生存率明显高于不表达S100A2的患者。多因素分析显示 S100A2表达、浸润深度、淋巴管及静脉浸润、淋巴结转移、TNM 分期是胃癌患者预后的独立因素。结论：在胃炎-肠上皮化生-胃癌过程中 S100A2 mRNA 和蛋白表达逐渐降低。S100A2表达与肿瘤大小、浸袭深度、淋巴管和静脉侵犯、淋巴结转移及 TNM 分期负相关，并随胃癌分化程度降低，S100A2的阳性表达率逐渐降低。S100A2表达是独立的胃癌预后预测因素，是胃癌患者预后良好的指标之一。%Objective:To study the relationship between S100A2 expressiol in chronic gastritis,intestinal metapla-sia,gastric cancer and clinical characteristics. Methods:HE staining was used for gastric specimens histopathological diagnosis. Using immunohistochemistry to detect the expression of tissue S100A2 protein. qRT - PCR was used to de-tect mRNA expression of S100A2 gene. Western blot for S100A2 gene encoding protein. Kaplan - Meier survival curves were used to distinguish and compare survival. Results:S100A2,S100A2 mRNA expression levels were in the following descending order:Gastritis,intestinal metaplasia and carcinoma(P < 0. 001). Immunohistochemical analysis of S100A2 expression:S100A2 was detected in gastritis(Gas),intestinal metaplasia(IM)and cancer(Ca)cytoplas-mic expression. Overall,S100 A2 expression results for gastritis cases 100%(73 / 73),90. 7% IM cases(78 /86),48. 9% of gastric cancer cases(170 / 348)(P < 0. 001). In gastric cancer,the lack of S100A2 protein in elderly patients than in young patients. S100A2 protein expression and tumor size,depth of invasion,lymphatic and venous in-vasion,lymph node metastasis,TNM stage in cancer patients was negatively correlated,the positive rate of S100A2 ex-pression were 65. 9% in highly,56. 4% in moderately and 17. 2% in poorly differentiated gastric carcinoma respec-tively(P < 0. 05),but no correlation between gender and patients(P > 0. 05). Kaplan - Meier analysis of cumulative survival showed:Weak or moderate expressions of S100A2 gene survival were significantly higher than patients without S100A2 expression. Multivariate analysis showed that,S100 A2 expression,depth of invasion,lymphatic and venous invasion,lymph node metastasis,TNM staging of gastric cancer were independent poor prognostic factors. Conclusion:The expression of S100A2 is a more favorable prognostic factor in patients with gastric cancer. Cox proportional haz-ards analysis,multivariate analysis showed that the depth of tumor invasion,lymphatic or venous invasion,lymph node metastasis,distant metastasis,TNM stage and S100A2 expression are independent prognostic factors in patients with gastric cancer. The positive rate of S100A2 expression decreased by the degree of differentiation of gastric carcinoma. These results suggest that S100A2 is an independent prognostic factor in gastric cancer,and can be used as a molecu-lar marker distinguished two types of cancer.