S100A8和S100A9在幽门螺杆菌相关胃炎中的表达及其临床意义

Expression and clinical significance of S100A8 and S100A9 in Helicobacter pylori associated gastritis

目的探讨S100A8和S100A9在H.pylori相关胃炎中的表达及其临床意义。方法选择2018年10月至2019年5月在山西医科大学第一医院确诊的慢性胃炎患者101例。采用免疫组织化学法检测101例慢性胃炎患者胃黏膜组织中S100A8和S100A9的表达(以吸光度表示),同时采用RT-PCR法检测其中48例患者胃黏膜组织S100A8和S100A9的mRNA表达,并结合H-E染色病理诊断和临床H.pylori感染资料进行分析。统计学方法采用Mann-WhitneyU检验、Kruskal-WallisH检验和Spearman秩相关。结果 101例患者中,慢性萎缩性胃炎(CAG)59例(CAG组),慢性非萎缩性胃炎(NAG)42例(NAG组);H.pylori阳性59例(H.pylori阳性组),H.pylori阴性42例(H.pylori阴性组)。CAG组S100A8和S100A9的表达水平与NAG组比较[分别为0.10(0.07,0.13)比0.09(0.06,0.10)和0.13(0.08,0.15)比0.09(0.07,0.10)],以及H.pylori阳性组S100A8和S100A9的表达水平与H.pylori阴性组比较[分别为0.11(0.10,0.13)比0.07(0.06,0.08)和0.13(0.10,0.15)比0.07(0.07,0.08)],差异均有统计学意义(U=754.00、602.00、5.00、40.00,P均<0.01)。CAG组中H.pylori阳性患者(34例)S100A8和S100A9的表达水平与阴性患者(25例)比较[分别为0.13(0.11,0.14)比0.07(0.07,0.08)和0.15(0.14,0.16)比0.08(0.08,0.09)],以及NAG组中H.pylori阳性患者(25例)的S100A8和S100A9的表达水平与阴性患者(17例)比较[分别为0.10(0.09,0.10)比0.06(0.05,0.07)和0.10(0.10,0.11)比0.07(0.06,0.07)] ,差异均有统计学意义(U=1.00、0.00、0.00、0.00,P均<0.01)。CAG合并H.pylori感染者的S100A8和S100A9的表达水平最高,NAG无H.pylori感染者的S100A8和S100A9表达水平最低,差异均有统计学意义(H=84.78、89.64,P均<0.01)。CAG患者(24例)S100A8和S100A9的mRNA表达水平与NAG患者(24例)比较[分别为0.12(0.06,1.31)比0.05(0.03,0.08)和0.19(0.03,0.43)比0.03(0.01,0.09)],以及H.pylori阳性患者(24例)S100A8和S100A9的mRNA表达水平与阴性患者(24例)比较[分别为0.45(0.10,1.90)比0.05(0.03,0.08)和0.36(0.24,0.81)比0.03(0.01,0.04)],差异均有统计学意义(U=55.00、74.00、19.00、2.00,P均<0.05)。CAG合并H.pylori阳性患者(12例)S100A8和S100A9的mRNA表达水平与阴性患者(12例)比较[分别为0.85(0.27,2.28)比0.06(0.03,0.09)和0.39(0.25,0.87)比0.03(0.02,0.05)],以及NAG合并H.pylori阳性患者(12例)S100A8和S100A9的mRNA表达水平与阴性患者(12例)比较[分别为0.09(0.05,0.28)比0.04(0.03,0.07)和0.20(0.09,0.65)比0.01(0.01,0.03),差异均有统计学意义(U=5.00、2.00、0.00、0.00,P均<0.01)。CAG合并H.pylori感染者S100A8和S100A9的mRNA表达水平最高,NAG无H.pylori感染者的S100A8和S100A9的mRNA表达水平最低,差异均有统计学意义(H=20.43、24.15,P均<0.01)。S100A8和S100A9无论在蛋白质水平还是在mRNA水平的表达均呈正相关(r=0.899和0.903,P均<0.01)。结论 S100A8和S100A9可能参与H.pylori感染胃黏膜的致炎过程并促使胃黏膜上皮细胞增殖紊乱的发生,是H.pylori导致胃黏膜固有腺体减少和CAG发生的可能机制之一。S100A8和S100A9有望作为CAG诊断、随访生物标志物和治疗的潜在靶点。

Objective To explore the expression and clinical significance of S100A8 and S100A9 in Helicobacter pylori(H.pylori)associated gastritis.Methods A total of 101 patients with chronic gastritis diagnosed in the First Hospital of Shanxi Medical University from October 2018 to May 2019 were selected.The expression levels of S100A8 and S100A9 in the gastric mucosa tissues of 101 patients with chronic gastritis were determined by immunohistochemistry(in absorbance),and the mRNA expression levels of S100A8 and S100A9 in the gastric mucosa tissues of 48 patients were detected by reverse transcription-polymerase chain reaction.And the results combined with pathological diagnosis of routine staining and clinical H.pylori infection data were analyzed.Mann-Whitney U test,Kruskal-Wallis H test and Spearman rank correlation were used for statistical analysis.Results Among 101 patients,there were 59 cases of chronic atrophic gastritis(CAG group)and 42 cases of chronic non-atrophic gastritis(NAG group);59 cases were H.pylori positive(H.pylori positive group)and 42 cases were H.pylori negative(H.pylori negative group).There were statistically significant differences in the expression levels of S100A8 and S100A9 between CAG group and NAG group(0.10,0.07 to 0.13 vs.0.09,0.06 to 0.10 and 0.13,0.08 to 0.15 vs.0.09,0.07 to 0.10,respectively),and between H.pylori positive group and H.pylori negative group(0.11,0.10 to 0.13 vs.0.07,0.06 to 0.08 and 0.13,0.10 to 0.15 vs.0.07,0.07 to 0.08,respectively)(U=754.00,602.00,5.00 and 40.00,all P<0.01).There were statistically significant differences in the expression levels of S100A8 and S100A9 between H.pylori positive patients(34 cases)and H.pylori negative patients(25 cases)in CAG group(0.13,0.11 to 0.14 vs.0.07,0.07 to 0.08 and 0.15,0.14 to 0.16 vs.0.08,0.08 to 0.09,respectively),similarly,there were significant differences in the expression levels of S100A8 and S100A9 between H.pylori positive patients(25 cases)and H.pylori negative patients(17 cases)in NAG group(0.10,0.09 to 0.10 vs.0.06,0.05 to 0.07 and 0.10,0.10 to 0.11 vs.0.07,0.06 to 0.07,respectively)(U=1.00,0.00,0.00 and 0.00,all P<0.01).The results indicated that the expression levels of S100A8 and S100A9 were high in H.pylori positive patients in CAG group,the expression levels of S100A8 and S100A9 were low in H.pylori negative patients in NAG group,and the differences were statistically significant(H=84.78 and 89.64,both P<0.01).There were statistically significant differences in the expression of S100A8 and S100A9 at mRNA level between CAG group(24 cases)and NAG group(24 cases)(0.12,0.06 to 1.31 vs.0.05,0.03 to 0.08;0.19,0.03 to 0.43 vs.0.03,0.01 to 0.09),and the expression of S100A8 and S100A9 at mRNA level was significant between H.pylori positive patients(24 cases)and H.pylori negative patients(24 patients)(0.45,0.10 to 1.90 vs.0.05,0.03 to 0.08 and 0.36,0.24 to 0.81 vs.0.03,0.01 to 0.04)(U=55.00,74.00,19.00 and 2.00,all P<0.05).There were statistically significant differences in the expression of S100A8 and S100A9 at mRNA level between H.pylori positive patients(12 cases)and H.pylori negative patients(12 cases)of CAG group(0.85,0.27 to 2.28 vs.0.06,0.03 to 0.09 and 0.39,0.25 to 0.87 vs.0.03,0.02 to 0.05),and the expression of S100A8 and S100A9 at mRNA level was significant between H.pylori positive patients(12 cases)and H.pylori negative patients(12 cases)of NAG group(0.09,0.05 to 0.28 vs.0.04,0.03 to 0.07 and 0.20,0.09 to 0.65 vs.0.01,0.01 to 0.03)(U=5.00,2.00,0.00 and 0.00,all P<0.01).The results showed that the expression of S100A8 and S100A9 at mRNA level was high in H.pylori positive patients in CAG group,the expression of S100A8 and S100A9 at mRNA level was low in H.pylori negative patients in NAG group,and the differences were statistically significant(H=20.43 and 24.15,both P<0.01).The expression levels of S100A8 and S100A9 were positively correlated at both protein level and mRNA level(r=0.899 and 0.903,both P<0.01).Conclusions S100A8 and S100A9 may involve in the inflammation process of H.pylori-infected gastric mucosa and promote the proliferation of gastric epithelial cells,which may be one of mechanisms of intrinsic glands reduction and CAG genesis.S100A8 and S100A9 are expected to be potential biomarkers for diagnosis and follow-up and potential targets for treatmert of CAG.