胃癌并发Hp感染患者血清miR-101,HSP-70,IL-1β表达水平与肿瘤增殖和侵袭力的相关性研究

Serum miR-101,HSP-70 and IL-1 β in Gastric Cancer Patients with Hp Infection Correlation between Expression Level and Tmor Proliferation and Invasion

目的 探讨胃癌并发幽门螺杆菌(Helicobacter pylori,Hp)感染患者血清mi R-101,热休克蛋白-70(heat shock protein-70,HSP-70)和白细胞介素-1β(Interleukin-1β,IL-1β)表达水平与肿瘤增殖和侵袭力的相关性。方法 选取2017年2月~2020年2月绵阳市第三人民医院胃癌患者120例为观察组(依据Hp检测结果分为胃癌Hp阳性组68例、胃癌Hp阴性组52例)、同期慢性胃炎患者86例为对照组。测定比较各组血清miR-101,HSP-70,IL-1β水平和Hp感染U值,分析Hp感染与胃癌患者血清各指标水平关联性,统计胃癌Hp阳性组不同血清各指标水平患者胃癌组织中肿瘤增殖基因[磷脂酰肌醇-3激酶催化亚基δ(phosphatidylinositol-3 kinase catalytic subunit δ,PIK3CD)、C-myc癌基因(C-myc oncogene,C-myc)、zeste基因增强子同源物2(zeste gene enhancer homolog 2,EZH2)]、侵袭基因[泛素样含PHD和环指域1(Ubiquitin-like containing PHD and ring finger domain 1, UHRF1)及Vav3癌基因(Vav3oncogene,Vav3)]表达,分析胃癌并发Hp感染患者血清各指标水平与胃癌组织中肿瘤增殖、侵袭基因表达关系以及对患者生存率的影响。结果 胃癌Hp阳性组血清miR-101水平低于胃癌Hp阴性组、对照组(0.51±0.13 vs 0.82±0.16,1.38±0.29);HSP-70(2.73±0.69 pg/L vs 1.80±0.57 pg/L, 1.14±0.38 pg/L),IL-1β(42.07±18.54 pg/L vs 23.61±10.38 ng/L,16.37±7.09 ng/L)水平和Hp感染U值(246.59±31.28 dpm/mmol vs 59.26±12.68 dpm/mmol, 41.35±8.39 dpm/mmol)高于胃癌Hp阴性组、对照组,差异均有统计学意义(F=79.650~2 297.784,均P <0.05);Hp感染U值与胃癌Hp阳性组患者血清mi R-101(r=-0.629)水平呈负相关,与HSP-70(r=0.574)和IL-1β(r=0.539)水平呈正相关(均P <0.05);miR-101高水平患者组织中PIK3CD,C-myc,EZH2,UHRF1和Vav3基因表达量均低于低水平患者,差异有统计学意义(t=8.554~17.034,均P <0.05);HSP-70高水平患者组织中各基因表达量均高于HSP-70低水平患者,差异均有统计学意义(t=6.395~13.742,均P <0.05);IL-1β高水平患者组织中各基因表达量均高于IL-1β低水平患者,差异有统计学意义(t=5.330~21.755,均P <0.05)。胃癌Hp阳性患者血清miR-101水平与组织中PIK3CD,C-myc,EZH2,UHRF1和Vav3基因表达量呈负相关(r=-0.664,-0.709,-0.714,-0.702,-0.687),HSP-70和IL-1β水平与组织中各基因表达量呈正相关(r=0.608~0.702,均P <0.05)。随访至2021年2月,经Kaplan-Meier生存分析显示,HSP-70和IL-1β高水平胃癌Hp阳性患者生存率均低于HSP-70和IL-1β低水平患者,miR-101高水平患者生存率高于低水平患者,差异有统计学意义(χ^(2)=8.163~9.862,均P <0.05)。结论 胃癌患者并发Hp感染可诱导血清miR-101,HSP-70和IL-1β异常表达,促进肿瘤增殖和侵袭,影响患者预后。

Objective To investigate correlation between expression level and tumor proliferation and invasiveness of the serum miR-101, heat shock protein-70(HSP-70) and interleukin-1β(Interleukin-1β, IL-1β) in patients with gastric cancer complicated by Helicobacter pylori(Hp) infection. Methods From February 2017 to February 2020, 120 patients with gastric cancer in the Third People’s Hospital of Mianyang City were selected as the observation group.According to the Hp test results, they were divided into 68 patients in gastric cancer Hp positive group and 52 patients in gastric cancer Hp negative group and 86 cases of the control group. Serum miR-101, HSP-70 and IL-1 β level were measured and compared and Hp infection U value,and analyzed the correlation between Hp infection and serum index levels in patients with gastric cancer, and counted the tumor proliferation gene [Phosphatidylinositol-3 kinase catalytic subunitδ(PIK3CD), C-myc oncogene(C-myc), zeste gene enhancer homolog 2(EZH2)], invasion gene [Ubiquitin-like containing PHD and ring finger domain 1(UHRF1) and Vav3 oncogene(Vav3)] expression.Analyzed the relationship between serum index levels and tumor proliferation, invasive gene expression in gastric cancer patients with HP infection, as well as the effect on the survival rate of patients. Results The serum miR-101 level of gastric cancer Hp positive group was lower than that of gastric cancer Hp negative group and control group(0.51±0.13 vs 0.82±0.16, 1.38±0.29). HSP-70(2.73±0.69 pg/L vs 1.80±0.57 pg/L, 1.14±0.38 pg/L), IL-1β levels(42.07±18.54 pg/L vs 23.61±10.38 ng/L, 16.37±7.09 ng/L) and Hp infection U value(246.59±31.28 dpm/mmol vs 59.26±12.68 dpm/mmol, 41.35±8.39 dpm/mmol) were higher than gastric cancer Hp negative group and control group. The differences were statistically significant( F=79.650~2 297.784, all P < 0.05). Hp infection U value was negatively correlated with serum miR-101(r=-0.629) level in patients with gastric cancer Hp positive group, and was negatively correlated with HSP-70(r=0.574) and IL-1β(r=0.539) levels were positively correlated(all P<0.05). PIK3CD, C-myc, EZH2, UHRF1 and Vav3 gene expression in the tissues of patients with high miR-101 levels were all lower than those of patients with low levels, and the differences were statistically significant(t=8.554~17.034, all P<0.05).The expression of each gene in the tissues of HSP-70 highlevel patients was higher than that of HSP-70 low-level patients, and the difference was statistically significant(t= 6.395~13.742, all P <0.05). The expression of each gene in the tissues of patients with high IL-1β levels was higher than that in patients with low IL-1β levels, and the differences were statistically significant(t=5.330~21.755, all P<0.05). The level of serum miR-101 in HP positive patients with gastric cancer was negatively correlated with the expression of PIK3CD, C-myc, EZH2, UHRF1 and Vav3 genes in the tissue(r=-0.664.-0.709,-0.714,-0.702,-0.687), and the levels of HSP-70 and IL-1β were positively correlated with the expression of each gene in the tissue(r=0.608~0.702, all P<0.05). Follow-up by February 2021, Kaplan-Meier survival analysis showed that the survival rate of HSP-positive patients with gastric cancer with high levels of HSP-70 and IL-1β was lower than that of patients with HSP-70, low levels of IL-1β and patients with high levels of miR-101. The rate was higher than that of low-level patients, and the difference was statistically significant(χ^(2)=8.163~9.862, all P<0.05). Conclusion Patients with gastric cancer combined with Hp infection can induce the abnormal expression of serum miR-101, HSP-70 and IL-1β, promote tumor proliferation and invasion, and affect the prognosis of patients.