[1]王　允,申重阳,韩建军,等.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[J].现代检验医学杂志,2022,37(02):17-22.[doi:10.3969/j.issn.1671-7414.2022.02.004]
　WANG Yun,SHEN Chong-yang,HAN Jian-jun,et al.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[J].Journal of Modern Laboratory Medicine,2022,37(02):17-22.[doi:10.3969/j.issn.1671-7414.2022.02.004]
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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()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年02期
页码:
17-22
栏目:
论　著
出版日期:
2022-03-15

文章信息/Info

Title:
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
文章编号:
1671-7414（2022）02-017-07
作者:
王　允1; 申重阳2; 韩建军1; 贾　利1; 高　飞1; 何　君1; 闵燕梅1
(1. 绵阳市第三人民医院/ 四川省精神卫生中心肿瘤内科，四川绵阳 621000；2. 成都中医药大学基础医学院，成都 610041)
Author(s):
WANG Yun1;  SHEN Chong-yang2;  HAN Jian-jun1;  JIA Li1;  GAO Fei1;  HE Jun1;  MIN Yan-mei1
（1.Department of Oncology, the Third People’s Hospital of Mianyang/Sichuan Mental Health Center, Sichuan Mianyang 621000, China; 2.School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610041,China）
关键词:
胃癌; Hp感染; miR-101; 热休克蛋白-70; 白细胞介素-1β; 肿瘤增殖; 肿瘤侵袭
分类号:
735.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2022.02.004
文献标志码:
A
摘要:
目的　探讨胃癌并发幽门螺杆菌（Helicobacter pylori，Hp）感染患者血清miR-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miR-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（χ2=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。
Abstract:
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 (χ2=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.

参考文献/References:

[1] 杨民连. 胃癌患者预后影响因素分析[J]. 中国药物与临床, 2018, 18(12):2154-2156. YANG Minlian. Analysis of prognostic factors in patients with gastric cancer[J]. Chinese Remedies & Clinics,2018,18(12):2154-2156.
[2] FITZGERALD T L, EFIRD J T, BELLAMY N, et al. Perioperative chemotherapy versus postoperative chemoradiotherapy in patients with resectable gastric/ gastroesophageal junction adenocarcinomas: A survival analysis of 5 058 patients[J]. Cancer, 2017, 123(15): 2909-2917.
[3] 张海云, 蔡晓波, 郭宝明, 等．胃癌患者Hp 感染与 CyclinD1, NF-kb, Beclin1 表达及临床病理特征的关 系分析[J]. 中国实验诊断学, 2020, 24(5):773-776． ZHANG Haiyun,CAI Xiaobo,GUO Baoming,et al. Analysis of the relationship between Hp infection and expressions of CyclinD1, NF-kb, Beclin1 and clinicopathological features in patients with gastric cancer[J]. Chinese Journal of Laboratory Diagnosis ,2020,24(5):773-776.
[4] 刘涛, 李睿, 龚琳, 等． 胃幽门螺杆菌感染后 Semaphorin 5A 致胃癌可能机制的研究[J]．分子诊 断与治疗杂志,2019,11(3):189-193. LIU Tao,LI Rui,GONG Lin,et al. Study on the mechanism of gastric cancer induced by Semaphorin 5A after Helicobacter pylori infection[J]. Journal of Molecular Diagnosis and Therapy,2019,11(3):189-193.
[5] SULTANA Z, BANKURA B, PATTANAYAK A K, et al. Association of interleukin-1 beta and tumor necrosis factor-alpha genetic polymorphisms with gastric cancer in India[J]. Environmental and Molecular Mutagenesis, 2018, 59(7): 653-667.
[6] SAINI J, SHARMA P K. Clinical, prognostic and therapeutic significance of heat shock proteins in cancer[J]. Current Drug Targets, 2018, 19(13): 1478- 1490.
[7] 中华医学会消化内镜学分会, 中国抗癌协会肿瘤 内镜专业委员会．中国早期胃癌筛查及内镜诊治 共识意见(2014 年, 长沙)[J]. 中华消化杂志, 2014, 34(7):433-448. Chinese Society of Digestive Endoscopy, Chinese Medical Association,the Society of Tumor Endoscopy Chinese Anti Cancer Association. Committee of Chinese consensus on screening and endoscopic diagnosis and treatment of early gastric cancer in China(Changsha,2014)[J]. Chinese Journal of Digestion,2014,34(7):433-448.
[8] 中华医学会消化病学分会, 房静远, 刘文忠, 等．中 国慢性胃炎共识意见(2012 年, 上海)[J]. 中华消化 杂志, 2013, 33(1)：5-16． Chinese Society of Gastroenterology, FANG Jingyuan, LIU Wenzhong,et al. Chinese consensus on chronic gastritis (2012, Shanghai)[J]. Chinese Journal of Digestion ,2013,33(1):5-16.
[9] 郭辉, 程广坤, 张晓雪, 等．幽门螺旋杆菌感染与 胃癌患者血清IL-1β, IL-8, IL-32 的关系[J]. 海南医 学,2020,31(18):2326-2329. GUO Hui,CHENG Guangkun,ZHANG Xiaoxue,et al. Relationship between Helicobacter pylori infection and serum IL-1β, IL-8,I L-32 in patients with gastric cancer [J]. Hainan Medical Journal,2020,31(18):2326-2329.
[10] CHOI I J, KIM C G, LEE J Y, et al. Family history of gastric cancer and Helicobacter pylori treatment[J]. The New England Journal of Medicine, 2020, 382(5): 427-436.
[11] SUZUKI H, MORI H. Gastric cancer after Helicobacter pylori eradication[J]. Gan to Kagaku Ryoho. Cancer & Chemotherapy, 2018, 45(8): 1123-1127.
[12] KIM H J, KIM N, PARK J H, et al. Helicobacter pylori eradication induced constant decrease in interleukin- 1B expression over more than 5 years in patients with gastric cancer and dysplasia[J]. Gut and Liver, 2020, 14(6): 735-745.
[13] 杜三军, 张娅娟, 孙晓冉, 等．幽门螺旋杆菌感染与 胃癌患者血清IL-32, IL-1β, TNF-α 的关系研究[J]. 现代生物医学进展, 2019, 19(24)：4740-4743. DU Sanjun,ZHANG Yajuan,SUN Xiaoran,et al. Study on the relationship between Helicobacter pylori infection and serum IL-32, IL-1β and TNF-α in patients with gastric cancer[J]. Progress in Modern Biomedicine, 2019,19(24):4740-4743.
[14] WU Yujiao, SHEN Li, LIANG Xiuming, et al. Helicobacter pylori-induced YAP1 nuclear translocation promotes gastric carcinogenesis by enhancing IL-1β expression[J]. Cancer Medicine, 2019, 8(8): 3965- 3980.
[15] 魏茜, 余树林, 黄宜峰．胃癌组织中P53, IL-1β, NF-κB 的表达及与幽门螺杆菌感染的相关性分析 [J]. 中国中西医结合消化杂志, 2019, 27(3)：228- 231. WEI Qian,YU Shulin,HUANG Yifeng. Analysis of expression of P53, IL-1β and NF-κB in gastric cancer and its correlation with Helicobacter pylori infection[J]. Chinese Journal of Integrated Traditional and Western Medicine on Digestion,2019,27(3):228-231.
[16] 张德志, 刘猛, 季节．血清IL-8 和IL-1β 在胃癌 患者中的水平变化及临床意义[J]．中国卫生工程 学,2020,19(1):69-71. ZHANG Dezhi,LIU Meng,JI Jie. Serum IL-8 and IL- 1β in patients with gastric cancer of level changes and clinical significance [J]. Chinese Journal of Public Health Engineering,2020,19(1):69-71.
[17] 付保芹, 郭成香, 王珊珊, 等. 胃癌患者血清miR- 204, HSP-70 及IL-2 与Hp 感染及病情关系研究[J]. 中华医院感染学杂志, 2020, 30(7):1012-1015. FU Baoqin,GUO Chengxiang,WANG Shanshan,et al. The correlation between serum miR-204,HSP-70 and IL-2 expression and the illness progression in patients with gastric cancer [J].Chinese Journal of Nosocomiology, 2020,30(7):1012-1015.
[18] 王琼, 肖葛琼, 吕秋琼, 等．胃癌患者幽门螺杆菌感 染与NF-κB 和CCL20 及HSP70 表达的关系[J]. 中 华医院感染学杂志, 2018, 28(20)：3064-3067, 3071. WANG Qiong,XIAO Geqiong,LU Qiuqiong,et al. Relationship between Helicobacter pylori infection and NF-κB ,CCL20 and HSP70 expression in patients with gastric cancer[J]. Chinese Journal of Nosocomiology, 2018,28(20):3064-30673071.
[19] TENG F, XU Z Y, LYU H, et al. Triptolide reverses apatinib resistance in gastric cancer cell line MKN45 via inhibition of heat shock protein 70[J]. Chinese Journal of Oncology, 2018, 40(2): 92-98.
[20] 缪孟郡, 方志红, 程菁祎．胃癌患者血清趋化因子 L20, 热休克蛋白70 的表达及意义[J]. 医学临床研究, 2019, 36(12)：2346-2348． MIAO Mengjun, FANG Zhihong, CHENG Qingyi. Serum levels and clinical significance of CCL20 and HSP70 in patients with gastric cancer[J]. Journal of Clinical Research,2019,36(12):2346-2348.
[21] 赵格, 高琼, 余宗涛, 等．肺癌患者血浆miR-3151 表达水平与临床病理特征的相关性研究[J]. 现代检 验医学杂志, 2020, 35(5):28-32. ZHAO Ge,GAO Qiong,YU Zongtao,et al. Study on the correlation between the expression of miR-3151 in plasma and clinicopathological features in patients with lung cancer[J]. Journal of Modern Laboratory Medicine,2020,35(5):28-32.
[22] 黄光墉, 王金生．miR-101 和miR-25 表达水平对胃 癌诊断效果及手术前后变化研究[J]. 标记免疫分析 与临床, 2019, 26(10):1720-1722, 1740. HUANG Guangyong,WANG Jinsheng. The diagnostic significance of miR-101 and miR-25 expression levels on gastric cancer and their changes before and after operation[J].Labeled Immunoassays and Clinical Medicine ,2019,26(10):1720-1722,1740.
[23] 冯玉梅, 李思颖．血清miR-101 与miR-25 在胃癌 手术患者中的检测价值[J]. 检验医学与临床, 2018, 15(1):119-121. FENG Yumei,LI Siying.Detection value of serum miR-101 and miR-25 in patients undergoing gastric cancer surgery[J].Laboratory Medicine and Clinical,2018,15(1):119-121.

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　CHEN Xu-yanga,JI Mao-lib,LIU Xue-huab,et al.Differential Diagnosis of Gastric Cancer and Gastric Ulcer by Joint Detection of Peripheral Blood MPV，PDW and Serum[J].Journal of Modern Laboratory Medicine,2019,34(02):107.[doi:10.3969/j.issn.1671-7414.2019.01.028]
[9]张筱东,谢星星,李　佳,等.血清外泌体 miR-221 和 miR-378 水平检测在胃癌诊断中的应用研究[J].现代检验医学杂志,2020,35(06):52.[doi:doi:10.3969/j.issn.1671-7414.2020.06.013]
　ZHANG Xiao-dong,XIE Xing-xing,LI Jia,et al.Application Study of Serum Exosome miR-221 and miR-378 Detection in theDiagnosis of Gastric Cancer[J].Journal of Modern Laboratory Medicine,2020,35(02):52.[doi:doi:10.3969/j.issn.1671-7414.2020.06.013]
[10]徐翠香,王建华,武　敏,等.胃癌患者血清CA724，NSE和 PGR水平联合检测对肿瘤临床病理分期及淋巴结转移的诊断价值[J].现代检验医学杂志,2021,36(01):6.[doi:10.3969/j.issn.1671-7414.2021.01.002]
　XU Cui-xiang,WANG Jian-hua,WU Min,et al.Diagnostic Value of Combined Detection of Serum CA724, NSE and PGR Levels in Patients with Gastric Cancer for Tumor Clinical Pathological Stage and Lymph Node Metastasis[J].Journal of Modern Laboratory Medicine,2021,36(02):6.[doi:10.3969/j.issn.1671-7414.2021.01.002]

备注/Memo

备注/Memo:
基金项目：四川省科技计划项目2018JDR2653。
作者简介：王允（1977-），女，本科，副主任医师，研究方向：消化道恶性肿瘤和妇科恶性肿瘤，E-mial:hhkst56@163.com。
更新日期/Last Update: 1900-01-01