胃癌病灶内幽门螺杆菌感染与病理特征、凋亡侵袭基因和PI3K/AKT信号通路的关系
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摘要
目的 探讨胃癌病灶内幽门螺杆菌(H.pylori)感染与病理特征、凋亡侵袭基因、PI3K/AKT信号通路的相关性。方法 选择我院2016年9月至2019年1月间经胃镜检查、病灶组织病理学证实为原发性胃癌的患者117例作为胃癌组,选择同期在我院进行胃镜检查并明确无恶性病变的志愿者100例为非胃癌组。检测两组对象H.pylori阳性情况并进一步分为Hp阳性组(n=59)和Hp阴性组(n=58)。对比不同H.pylori感染情况胃癌患者的病理特征及病灶组织中凋亡侵袭基因、PI3K/AKT信号通路相关分子的表达差异。结果 胃癌组患者H.pylori感染率显著高于非胃癌组(P<0.05)。H.pylori阳性组中肿瘤直径≥5 cm、TNM分期为Ⅲ～Ⅳ期、组织分化程度为低—中分化和淋巴结转移的比例均显著高于Hp阴性组患者,差异均有统计学意义(P<0.05)。Hp阳性组患者胃癌病灶中凋亡相关基因p53、Bax的表达量低于Hp阴性组,Survivin、Bcl-2的表达量高于Hp阴性组;侵袭相关基因BOP1、MUC17、SIRT2 mRNA的表达量高于Hp阴性组(P<0.05)。Hp阳性组患者胃癌病灶中PI3K/AKT信号通路相关分子PI3K和AKT的表达量高于Hp阴性组(P<0.05)。结论 胃癌合并H.pylori感染者的病情相对较重,可能与H.pylori能上调PI3K/AKT信号通路活性、影响癌细胞相关凋亡及侵袭基因的表达有关。
Objective To investigate the correlation of H. pylori infection with pathological features, apoptotic invasion genes and PI3 K/AKT signaling pathway in gastric cancer. Methods 117 patients with primary gastric cancer confirmed by histopathology in our hospital during September 2016 to January 2019 were selected as Gastric cancer group; 100 volunteers without malignant lesions were selected as Non-gastric cancer group. The positive rate of H. pylori was detected, based on which the Gastric cancer group was further divided into Hp-positive group(n=59) and Hp-negative group(n=58). The pathological characteristics of gastric cancer patients including their H. pylori infection, expression of apoptotic invasive genes and PI3 K/AKT signaling pathway related molecules in lesions were compared between groups. Results The infection rate of H. pylori in Gastric cancer group was significantly higher than that in Non-gastric cancer group(P<0.05). The rates of tumor diameter ≥5 cm, TNM stage III-IV, low-to-moderate tissue differentiation and lymph node metastasis in Hp-positive group were significantly higher than those in Hp-negative group respectively, the differences were statistically significant(P<0.05). The expressions of apoptosis-related genes p53 and Bax in gastric cancer lesions of Hp-positive group were lower than those of Hp-negative group, while the expressions of Survivin and Bcl-2 were higher than those of Hp-negative group, and the expressions of invasion-related genes BOP1, MUC17 and SIRT2 were higher than those of Hp-negative group(Ps<0.05). The expressions of PI3 K/AKT signaling pathway related molecules PI3 K and AKT in gastric cancer lesions of Hp-positive group were higher than those of Hp-negative group(Ps<0.05). Conclusion Gastric cancer with H. pylori infection is relatively more serious, which may be related to the up-regulation of PI3 K/AKT signaling pathway activity by H. pylori, and the influence of H. pylori on apoptosis and expression of invasive genes in cancer cells.
Objective To investigate the correlation of H. pylori infection with pathological features, apoptotic invasion genes and PI3 K/AKT signaling pathway in gastric cancer. Methods 117 patients with primary gastric cancer confirmed by histopathology in our hospital during September 2016 to January 2019 were selected as Gastric cancer group; 100 volunteers without malignant lesions were selected as Non-gastric cancer group. The positive rate of H. pylori was detected, based on which the Gastric cancer group was further divided into Hp-positive group(n=59) and Hp-negative group(n=58). The pathological characteristics of gastric cancer patients including their H. pylori infection, expression of apoptotic invasive genes and PI3 K/AKT signaling pathway related molecules in lesions were compared between groups. Results The infection rate of H. pylori in Gastric cancer group was significantly higher than that in Non-gastric cancer group(P<0.05). The rates of tumor diameter ≥5 cm, TNM stage III-IV, low-to-moderate tissue differentiation and lymph node metastasis in Hp-positive group were significantly higher than those in Hp-negative group respectively, the differences were statistically significant(P<0.05). The expressions of apoptosis-related genes p53 and Bax in gastric cancer lesions of Hp-positive group were lower than those of Hp-negative group, while the expressions of Survivin and Bcl-2 were higher than those of Hp-negative group, and the expressions of invasion-related genes BOP1, MUC17 and SIRT2 were higher than those of Hp-negative group(Ps<0.05). The expressions of PI3 K/AKT signaling pathway related molecules PI3 K and AKT in gastric cancer lesions of Hp-positive group were higher than those of Hp-negative group(Ps<0.05). Conclusion Gastric cancer with H. pylori infection is relatively more serious, which may be related to the up-regulation of PI3 K/AKT signaling pathway activity by H. pylori, and the influence of H. pylori on apoptosis and expression of invasive genes in cancer cells.
引文
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[15] Zheng S,Lv P,Su J,et al.Overexpression of CBX2 in breastcancerpromotes tumor progression through the PI3K/AKT signaling pathway[J].Am J Transl Res,2019,11(3):1668-1682.
[2] Noto JM,Rose KL,Hachey AJ,et al.Carcinogenic Helicobacter pylori strains selectively dysregulate the in vivo gastric proteome,which may be associated with stomach cancer progression[J].Mol Cell Proteomics,2019,18(2):352-371.
[3] Noto JM,Chopra A,Loh JT,et al.Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments[J].Gut,2018,67(10):1793-1804.
[4] Suarez G,Romero-Gallo J,Sierra JC,et al.Genetic manipulation of Helicobacter pylori virulence function by hostcarcinogenicphenotypes[J].Cancer Res,2017,77(9):2401-2412.
[5] Waldum HL,Hauso ?,S?rdal ?F,et al.Gastrin may mediate thecarcinogeniceffect of Helicobacter pylori infection of the stomach[J].Dig Dis Sci,2015,60(6):1522-1527.
[6] WEI Xiaodong,TANG Yanpin.Advances in research on the effect of Helicobacter pylori infection on DNA methylation in gastric cancer[J].Chin J Integr Chin West Med Surg,2018,24(6):803-805.(in Chinese) 魏晓东,唐艳萍.胃癌中幽门螺旋杆菌感染对DNA甲基化影响的研究进展[J].中国中西医结合外科杂志,2018,24(6):803-805.
[7] XING Zhifang,LUY Panpan.Research progress on the relationship between Helicobacter pylori and pathogenesis and treatment of gastric cancer[J].Lab Med Clin,2017,14(20):3123-3125.(in Chinese) 邢志芳,吕攀攀.幽门螺旋杆菌与胃癌致病机制及治疗方案相关性的研究进展[J].检验医学与临床,2017,14(20):3123-3125.
[8] Rahman MM,Sarker MAK,Hossain MM,et al.Association of p53 gene mutation with Helicobacter pylori infection in gastric cancer patients and its correlation with clinic pathological and environmental factors[J].World J Oncol,2019,10(1):46-54.
[9] Hou D,Che Z,Chen P,et al.Suppression of AURKA alleviates p27 inhibition on Bax cleavage and induces more intensive apoptosis in gastric cancer[J].Cell Death Dis,2018,9(8):781.
[10] Zhang Z,Kong Y,Yang W,et al.MicroRNA-218 enhances gastric cancer cell cisplatin sensitivity by targeting survivin[J].Exp Ther Med,2018,16(6):4796-4802.
[11] Li Q,Peng J,Liu T,et al.Effects of celecoxib on cell apoptosis and Fas,FasL and Bcl-2 expression in a BGC-823 human gastric cancer cell line[J].Exp Ther Med,2017,14(3):1935-1940.
[12] YANG Wenjuan,SONG Yin,ZHANG Ruixin,et al.MUC17 gene expression in gastric cancer tissues and cells and its effect on invasion and proliferation of gastric cancer cells[J].Shandong Med J,2018,58(39):1-4.(in Chinese) 杨文娟,宋莹,张瑞鑫,等.MUC17基因在胃癌组织、细胞中的表达及对胃癌细胞侵袭增殖能力影响[J].山东医药,2018,58(39):1-4.
[13] Xu L,Wang L,Zhou L,et al.The SIRT2/cMYC pathway inhibits peroxidation-related apoptosis in cholangiocarcinoma through metabolic reprogramming[J].Neoplasia,2019,21(5):429-441.
[14] CHEN Longyun,LIU Ye.Quercetin induces apoptosis of gastric cancer SGC7901 cells by inhibiting PI3K/AKT signaling pathway[J].Chin J Patho physiol,2018,34(11):1976-1980.(in Chinese) 陈龙云,柳叶.槲皮苷通过抑制PI3K/AKT信号通路诱导胃癌SGC7901细胞凋亡[J].中国病理生理杂志,2018,34(11):1976-1980.
[15] Zheng S,Lv P,Su J,et al.Overexpression of CBX2 in breastcancerpromotes tumor progression through the PI3K/AKT signaling pathway[J].Am J Transl Res,2019,11(3):1668-1682.