[1]蔡 梦,阎汉英,王晓静.血清LncRNA MALAT1 表达水平对EB 病毒感染相关胃癌的诊断和预后价值研究[J].现代检验医学杂志,2023,38(03):103-108.[doi:10.3969/j.issn.1671-7414.2023.03.018]
　CAI Meng,YAN Han-ying,WANG Xiao-jing.Diagnostic and Prognostic Value of Serum LncRNA MALAT1 Expression in Gastric Cancer Associated with Epstein-Barr Virus Infection[J].Journal of Modern Laboratory Medicine,2023,38(03):103-108.[doi:10.3969/j.issn.1671-7414.2023.03.018]
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血清LncRNA MALAT1 表达水平对EB 病毒感染相关胃癌的诊断和预后价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年03期
页码:
103-108
栏目:
论著
出版日期:
2023-05-15

文章信息/Info

Title:
Diagnostic and Prognostic Value of Serum LncRNA MALAT1 Expression in Gastric Cancer Associated with Epstein-Barr Virus Infection
文章编号:
1671-7414（2023）03-103-06
作者:
蔡 梦; 阎汉英; 王晓静
（河北北方学院附属第一医院消化内科，河北张家口 075000）
Author(s):
CAI Meng;  YAN Han-ying;  WANG Xiao-jing
（Department of Gastroenterology, the First Affiliated Hospital of Hebei North University，Hebie Zhangjiakou 075000, China）
关键词:
胃癌; EB 病毒相关胃癌; 肺腺癌相关转录物1
分类号:
R735.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2023.03.018
文献标志码:
A
摘要:
目的 探讨长链非编码RNAs（long non-coding RNAs，LncRNAs）肺腺癌相关转录物1（metastasis-associatedlung adenocarcinoma tran 1，MALAT1）在EB 病毒相关胃癌（EBV-associated gastric carcinoma，EBVaGC）患者血清中的表达及与患者预后的关系。方法 选取2015 年1 月～ 2017 年1 月河北北方学院附属第一医院消化内科收治的233 例胃癌患者为研究对象，根据EBV DNA 结果将患者分为EBV DNA 阳性组（n=123）和EBV DNA 阴性组（n=110）；同时选取在该院进行健康体检的志愿者100 例为对照组。实时荧光定量PCR（qRT-PCR）法检测血清LncRNA MALAT1水平；受试者工作特征（ROC）曲线分析LncRNA MALAT1 水平对EBVaGC 患者诊断的敏感度及特异度；利用Kaplan-Meier 法分析LncRNA MALAT1 表达与患者生存时间的关系；采用多因素COX 回归风险模型分析EBVaGC 患者的预后影响因素。结果 EBV DNA 阳性组EBVaGC 患者血清中LncRNA MALAT1 表达水平高于EBV DNA 阴性组和健康对照组（1.27±0.03 vs 1.12±0.05 ，0.96±0.04），差异有统计学意义（F=1620.239，P=0.000）；EBVaGC 患者血清中LncRNA MALAT1 表达与年龄、主癌位置、脉管癌栓、肿瘤直径、肿瘤组织学类型、神经侵犯、浸润深度无关（t=1.320 ～ 1.970，均P ＞ 0.05），与性别、分化程度、淋巴结转移、TNM 分期、Lauren 分型有关（t=4.880 ～ 29.748，均P=0.000）；ROC结果显示，LncRNA MALAT1 预测EBVaGC患者的曲线下面积（AUC）为0.863（95%CI：0.811 ～ 0.906），敏感度和特异度分别为92.68%，81.00%；Kaplan-Meier 分析结果显示，LncRNA MALAT1 高表达组患者五年累积生存率34.62%（27/78）显著低于低表达组57.78%（26/45），差异有统计学意义（Log rank χ2=6.944，P=0.008）；COX 结果显示，年龄、分化程度、淋巴结转移、TNM 分期、LncRNA MALAT1 高表达均是影响EBVaGC 患者生存状况的危险因素。结论 EBVaGC 患者血清中LncRNA MALAT1 表达水平上调，与EBV 感染相关胃癌的进展和预后密切相关，可作为诊断EBVaGC 患者的潜在血清标志物。
Abstract:
Objective To investigate the expression of long non-coding RNAs (LncRNAs) metastasis-assoliated lung adenocarcinoma tran 1 (MALAT1) in the sera of patients with EBV-associated gastric carcinoma (EBVaGC) and the relationship with patient prognosis. Methods A total of 233 patients with gastric admitted to the Department of Gastroenterology, the First Affiliated Hospital of Hebei North University from January 2015 to January 2017 were selected as the research objects. According to the EBV DNA results, the patients were divided into EBV DNA positive group (n=123) and EBV DNA negative group (n=110). At the same time, 100 healthy volunteers in the Department of Gastroenterology, the First Affiliated Hospital of Hebei North University were selected as the control group. Quantitative real-time PCR (qRT-PCR) method was performed to detect the level of serum LncRNA MALAT1. Subject work characteristic (ROC) curves to analyze the sensitivity and specificity of LncRNA MALAT1 levels for the diagnosis of EBVaGC patients. Kaplan-Meier method was performed to analyze the relationship between the expression of different LncRNA MALAT1 and the survival time of patients; multivariate COX regression risk model was performed to analyze the prognostic factors of EBVaGC patients. Results The expression level of LncRNA MALAT1 in serum of EBV DNA positive group was higher than that of EBV DNA negative group and healthy control group (1.27±0.03 vs 1.12±0.05，0.96±0.04), and the difference was statistically significant (F=1620.239, P=0000). The expression of LncRNA MALAT1 in serum of EBVaGC patients was not related to age, main tumor location, vascular tumor thrombus, tumor diameter, tumor histological type, nerve invasion, depth of invasion and location of occurrence (t=1.320 ～ 1.970, all P=0000), while was related to gender, degree of differentiation, lymph node metastasis, TNM stage and Lauren type (t=4.880 ～ 29.748, all P=0000). The ROC results showed that the AUC of LncRNA MALAT1 predicting EBVaGC was 0.863 (95%CI: 0.811 ～ 0.906), with a corresponding sensitivity and specificity of 92.68%, 81.00%, respectively. The results of Kaplan-Meier analysis showed that the 5-year cumulative survival rate of LncRNA MALAT1 high expression group was 34.62% (27/78), which was significantly lower than that of low expression group 57.78% (26/45), and the difference was statistically significant (Log rank χ2=6.944 , P=0.008). COX results showed that age, degree of differentiation, lymph node metastasis, TNM stage, and high expression of LncRNA MALAT1 were all risk factors affecting the survival of EBVaGC patients. Conclusion The up-regulation of LncRNA MALAT1 expression in serum of EBVaGC patients is closely related to the progression and prognosis of Epstein-Barr virus infector-associated gastric cancer, which may be used as a potential serum marker for the diagnosis of EBVaGC patients.

参考文献/References:

[1] QIU Miaozhen, HE Caiyun, LU Shixun, et al. Prospective observation: Clinical utility of plasma Epstein-Barr virus DNA load in EBV-associated gastric carcinoma patients[J]. International Journal of Cancer,2020, 146(1): 272-280.
[2] 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(2): 17-22, 36． WANG Yun, SHEN Chongyang, HAN Jianjun, 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(2): 17-22, 36.
[3] SONG Lusheng, SONG M, CAMARGO M C, et al. Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma[J]. Gastric Cancer, 2021, 24(4): 858-867.
[4] YANG Jing, LIU Zhifeng, ZENG Bin, et al. Epstein- Barr virus-associated gastric cancer: A distinct subtype[J]. Cancer Letters, 2020, 495: 191-199.
[5] HUI Dayang, CHEN Jianning, JIANG Ye, et al. CD44+CD24-/low sphere-forming cells of EBVassociated gastric carcinomas show immunosuppressive effects and induce Tregs partially through production of PGE2[J]. Experimental Cell Research, 2020, 390(2): 111968.
[6] ZHANG Jing, LI Xiaohan, HU Jingjin, et al. Long noncoding RNAs involvement in Epstein-Barr virus infection and tumorigenesis[J]. Virology Journal, 2020,17(1): 51.
[7] WANG Kehao, YU Xiaoyu, TAO Bilin, et al. Downregulation of LncRNA HCP5 has inhibitory effects on gastric cancer cells by regulating DDX21 expression[J]. Cytotechnology, 2021, 73(1): 1-11.
[8] ZHAO Cuiting, ZONG Zhihong, ZHU Qing, et al. The LncRNA MALAT1 participates in regulating coronary slow flow endothelial dysfunction through the miR- 181b-5p-MEF2A-ET-1 axis[J]. Vascular Pharmacology,2021, 138: 106841.
[9] 胡志立, 张明明．MALAT1 参与胃癌发生发展机制 的研究进展[J]．临床医学研究与实践, 2022, 7(1): 195-198． HU Zhili, ZHANG Mingming. Research progress on the mechanism of MALAT1 involved in the occurrence and development of gastric cancer[J]. Clinical Research and Practice, 2022, 7(1): 195-198.
[10] WANG Hanqing, ZHOU Lei, YANG Yang, et al. Screening and identification of key genes in EBVassociated gastric carcinoma based on bioinformatics analysis[J]. Pathology Research and Practice, 2021,222: 153439.
[11] WANG Zeyang, L? Zhi, XU Qian, et al. Identification of differential proteomics in Epstein-Barr virusassociated gastric cancer and related functional analysis[J]. Cancer Cell International, 2021, 21(1): 368.
[12] DONG Min, GONG Liping, CHEN Jianning, et al. EBV-miR-BART10-3p and EBV-miR-BART22 promote metastasis of EBV-associated gastric carcinoma by activating the canonical Wnt signaling pathway[J]. Cellular Oncology (Dordrecht), 2020,43(5): 901-913.
[13] XU Hao, ZHOU Jie, TANG Jin, et al. Identification of serum exosomal LncRNA MIAT as a novel diagnostic and prognostic biomarker for gastric cancer[J]. Journal of Clinical Laboratory Analysis, 2020, 34(8): e23323.
[14] 李超, 王辉, 洪建, 等. 胃癌组织LncRNA H19, miR- 141 表达变化及其与患者临床病理特征和预后的关 系[J]. 山东医药, 2019, 59(19): 5-9． LI Chao, WANG Hui, HONG Jian, et al. Expression changes of LncRNA H19 and miR-141 in gastric cancer tissues and their relationships with clinicopathological features and prognosis[J]. Shandong Medical Journal,2019, 59(19): 5-9.
[15] 王新庄, 孟建涛. 慢性心力衰竭患者血清LncRNA MALAT1 的表达水平及其临床意义[J]. 现代检验医 学杂志, 2022, 37(1): 141-144． WANG Xinzhuang, MENG Jiantao. Expression of LncRNA MALAT1 in peripheral blood of patients with chronic heart failure and its clinical significance[J]. Journal of Modern Laboratory Medicine, 2022, 37(1): 141-144.
[16] ZHANG Yunfei, LI Changsheng, ZHOU Yi, et al. Propofol facilitates cisplatin sensitivity via LncRNA MALAT1/miR-30e/ATG5 axis through suppressing autophagy in gastric cancer[J]. Life Sciences, 2020,244: 117280.
[17] 陈小丽, 黄达, 吴碧莹, 等.LncRNA MALAT1/miR- 101-3p/SMAD2 分子轴调控胶质瘤细胞上皮间质转 化的机制研究[J]. 中国免疫学杂志, 2021, 37(24): 3005-3009. CHEN Xiaoli, HUANG Da, WU Biying, et al. Mechanism of LncRNA MALAT1/miR-101-3p/ SMAD2 axis modulated epithelial mesenchymal transition of glioma cells[J]. Chinese Journal of Immunology, 2021, 37(24): 3005-3009.
[18] 杨珠兰, 郑丽澜, 陈玉芬．非编码RNA MALAT1 和 ANRIL 在卵巢癌患者组织中的表达情况及与临床病 理的关系[J]．中国性科学, 2021, 30(6): 49-51. YANG Zhulan, ZHENG Lilan, CHEN Yufen. Expressions of non-coding RNA MALAT1 and ANRIL in ovarian cancer tissues and their relationships with clinicopathology[J]. Chinese Journal of Human Sexuality, 2021, 30(6): 49-51.
[19] 孙永康, 颜学波, 朱泽民, 等. 长链非编码RNA MALAT1 在肝细胞癌发生发展中的作用[J]. 临床肝 胆病杂志, 2021, 37(3): 704-708． SUN Yongkang, YAN Xuebo, ZHU Zemin, et al. Role of long non-coding RNA MALAT1 in the development and progression of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2021, 37(3): 704-708.
[20] 马乐, 宫蔷, 李茜, 等. 长链非编码RNA MALAT1 对弥漫性大B 细胞淋巴瘤增殖、凋亡的影响[J]. 中 国细胞生物学学报, 2021, 43(9): 1803-1809. MA Le, GONG Qiang, LI Qian, et al. Effects of long non-coding RNA MALAT1 on proliferation and apoptosis of diffuse large B cell lymphoma[J]. Chinese Journal of Cell Biology, 2021, 43(9): 1803-1809.
[21] 丁立贤, 刘明, 李国东. 长链非编码RNA-MALAT1 在胃癌中的研究进展[J]. 肿瘤学杂志, 2020, 26(8): 665-668. DING Lixian, LIU Ming, LI Guodong. Research progress of long non-coding RNA-MALAT1 in gastric cancer[J]. Journal of Chinese Oncology, 2020, 26(8): 665-668.

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备注/Memo

备注/Memo:
基金项目：2021 年市级科技计划自筹经费项目（编号2121149D)。
作者简介：蔡梦（1984-），女，本科，护师，主要从事消化内科相关方向研究，E-mail：642518243@qq.com。
通讯作者：阎汉英（1993-），女，本科，护师，主要从事消化内科相关方向研究，E-mail：15369305716@163.com。
更新日期/Last Update: 2023-05-15