贝伐珠单抗辅助PD-1抑制剂治疗胃癌对血清miR-20a-5p和miR-515-3p的影响研究

汪斐; 刘佩; 胡楠

doi:10.19401/j.cnki.1007-3639.2024.05.006

您当前的位置：

首页 >

文章列表页 >

贝伐珠单抗辅助PD-1抑制剂治疗胃癌对血清miR-20a-5p和miR-515-3p的影响研究

论著 | 更新时间：2025-12-31

- 贝伐珠单抗辅助PD-1抑制剂治疗胃癌对血清miR-20a-5p和miR-515-3p的影响研究
- Effect of bevacizumab assisted PD-1 inhibitor on serum miR-20a-5p and miR-515-3p in the treatment of gastric cancer
- 中国癌症杂志 2024年34卷第5期页码：493-500
- 作者机构：
  
  南京医科大学第四附属医院肿瘤科，江苏南京 210000
- 作者简介：
  
  [ "汪斐（ORCID: 0009-0005-0513-5734），硕士，主治医师。" ]
  刘佩（ORCID: 0000-0003-2074-4376），硕士，副主任医师。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.05.006
  中图分类号： R735.2
- 收稿：2023-10-12，
  
  修回：2024-03-01，
  
  纸质出版：2024-05-30
- 稿件说明：
移动端阅览
汪斐, 刘佩, 胡楠. 贝伐珠单抗辅助PD-1抑制剂治疗胃癌对血清miR-20a-5p和miR-515-3p的影响研究[J]. 中国癌症杂志, 2024,34(5):493-500.

Fei WANG, Pei LIU, Nan HU. Effect of bevacizumab assisted PD-1 inhibitor on serum miR-20a-5p and miR-515-3p in the treatment of gastric cancer[J]. China Oncology, 2024, 34(5): 493-500.
汪斐, 刘佩, 胡楠. 贝伐珠单抗辅助PD-1抑制剂治疗胃癌对血清miR-20a-5p和miR-515-3p的影响研究[J]. 中国癌症杂志, 2024,34(5):493-500. DOI： 10.19401/j.cnki.1007-3639.2024.05.006.

Fei WANG, Pei LIU, Nan HU. Effect of bevacizumab assisted PD-1 inhibitor on serum miR-20a-5p and miR-515-3p in the treatment of gastric cancer[J]. China Oncology, 2024, 34(5): 493-500. DOI： 10.19401/j.cnki.1007-3639.2024.05.006.

摘要

背景与目的：

二线化疗方案治疗胃癌疗效欠佳，贝伐珠单抗属于抗血管生成分子靶向抗癌药物，信迪利单抗是一种国产的程序性死亡蛋白-1（programmed death-1，PD-1）抑制剂，两者结合是临床治疗胃癌的新方向。本研究旨在探究贝伐珠单抗辅助PD-1抑制剂治疗胃癌对血清miR-20a-5p和miR-515-3p的影响。

方法：

选取2019年1月—2021年7月于南京医科大学第四附属医院就诊的84例胃癌患者进行回顾性研究，根据治疗方案的不同将其分为观察组和对照组（每组各42例），对照组给予二线化疗方案治疗，观察组在对照组基础上给予贝伐珠单抗联合PD-1抑制剂（信迪利单抗）治疗，比较两组的客观缓解率（objective response rate，ORR）、疾病控制率（disease control rate，DCR）、血清肿瘤标志物、免疫功能指标、血清miR-20a-5p、miR-515-3p及不良反应总发生率。本研究已通过南京医科大学第四附属医院伦理委员会的伦理审批（批件号：20230531--K061）。

结果：

观察组的ORR（69.05%）和DCR（85.71%）均高于对照组（40.48%、64.29%）。观察组治疗后的血清糖类抗原12-5（carbohydrate antigen 12-5，CA12-5）、癌胚抗原（carcinoembryonic antigen，CEA）及细胞角蛋白19片段抗原21-1（cytokerantin-19-fragment antigen 21-1，CYFRA21-1）水平均低于对照组。观察组治疗后的CD4

T淋巴细胞、CD4

/CD8

淋巴细胞比值均高于对照组，CD8

T淋巴细胞低于对照组，差异均有统计学意义（

0.05）。观察组治疗后的血清miR-20a-5p、miR-515-3p水平均低于对照组，差异有统计学意义（

0.05）。观察组（28.57%）的不良反应总发生率与对照组（38.10%）相比，差异无统计学意义（

0.05）。

结论：

贝伐珠单抗辅助信迪利单抗可有效地提高胃癌治疗效率，改善免疫功能，降低血清miR-20a-5p、miR-515-3p及肿瘤标志物表达量，且不会增加不良反应，效果显著。

Abstract

Background and purpose:

Second-line chemotherapy is not effective in the treatment of gastric cancer. Bevacizumab is a molecularly targeted anticancer drug

and sindilizumab is a domestic programmed death-1 (PD-1) inhibitor. The combination of the two is a new direction for clinical treatment of gastric cancer. This study aimed to analyze the effects of bevacizumab assisted PD-1 inhibitor in the treatment of gastric cancer on serum miR-20a-5p and miR-515-3p.

Methods:

A retrospective study was conducted on 84 patients with gastric cancer treated in the Fourth Affiliated Hospital of Nanjing Medical University from January 2019 to July 2021

and they were divided into the observation group and the control group with 42 cases each according to different treatment plans. The control group was given second-line chemotherapy

and the observation group was given bevacizumab combined with PD-1 inhibitor (sindilizumab) on the basis of the control group. objective response rate (ORR)

disease control rate (DCR)

serum tumor markers

immune function indexes

serum miR-20a-5p and miR-515-3p levels and total incidence of toxic and side effects were compared between the two groups. This study has been approved by the Ethics Committee of the Fourth Affiliated Hospital of Nanjing Medical University (approval number: 20230531--K061).

Results:

The ORR (69.05%) and DCR (85.71%) of the observation group were higher than those of the control group (40.48% and 64.29%)

and the difference was statistically significant (

0.05). After treatment

serum carbohydrate antigen 1

2-5 (CA12-5)

carcinoembryonic antigen (CEA) and cytokerantin-19-fragment antigen 21-1 (CYFRA21-1) levels were lower in observation group than in control group (

0.05). CD4

T lymphocyte and CD4

/CD8

T lymphocyte ratio were higher in observation group than in control group after treatment (

0.05)

and CD8

T lymphocyte was lower in observation group than in control group after treatment (

0.05). After treatment

the serum levels of miR-20a-5p and miR-515-3p were lower in the observation group than in the control group (

0.05). There was no significant difference in total incidence of adverse effects between the observation group (28.57%) and the control group (38.10%) (

0.05).

Conclusion:

Bevacizumab assisted sindilizumab can effectively improve the treatment efficiency of gastric cancer

improve immune function

and reduce the expression levels of serum miR-20a-5p

miR-515-3p and tumor markers

without increasing toxic and side effects.

关键词

Keywords

references

黄萍 , 徐洪雨 . 白细胞介素-6在胃癌诊断、发展、治疗中的作用 [J ] . 胃肠病学和肝病学杂志 , 2021 , 30 ( 2 ): 207 - 211 .

HUANG P , XU H Y . The role of interleukin-6 in the diagnosis, development and treatment of gastric cancer [J ] . Journal of Gastroenterology and Hepatology , 2021 , 30 ( 2 ): 207 - 211 .

KOJIMA T , YAO K S , OHTSU K , et al. A comparative study of demarcation line diagnostic performance between non-magnifying observation with white light and non-magnifying observation with narrow-band light for early gastric cancer [J ] . Gastric Cancer , 2022 , 25 ( 4 ): 761 - 769 . DOI: 10.1007/s10120-022-01299-5 http://doi.org/10.1007/s10120-022-01299-5

肖聃 , 闻朋浩 , 张振 . PRKDC SAMHD1 miR-515-3p在进展期胃癌中的表达及与病理特征相关性研究 [J ] . 实用医技杂志 , 2022 , 29 ( 3 ): 249 - 253 .

XIAO D , WEN P H , ZHANG Z . Expression of PRKDC, SAMHD1 and miR-515-3p in advanced gastric cancer and correlation with pathology [J ] . J Pract Med Tech , 2022 , 29 ( 3 ): 249 - 253 .

马悦 . 胃癌患者血清miR-20a-5p、miR let-7a表达及其临床意义 [J ] . 胃肠病学和肝病学杂志 , 2022 , 31 ( 8 ): 902 - 907 .

MA Y . Expressions of miR-20a-5p and miR let-7a in gastric cancer patients and their clinical significance [J ] . Chin J Gastroenterol Hepatol , 2022 , 31 ( 8 ): 902 - 907 .

郭慧敏 , 张磊 , 王丽红 . MiR-125b-5p和miR-196a-5p在胃癌根治术后患者血清中的表达水平及其与临床病理参数和预后的关系 [J ] . 实用癌症杂志 , 2022 , 37 ( 2 ): 292 - 295 .

GUO H M , ZHANG L , WANG L H . The expression levels of serum miR-125b-5p and miR-196a-5p in patients after radical gastric cancer surgery and their relationship with clinicopathological parameters and prognosis [J ] . Pract J Cancer , 2022 , 37 ( 2 ): 292 - 295 .

刘汉屈 , 张燕芳 , 张帆 , 等 . 血清miR-124-3p、miR-361-5p与晚期胃癌患者临床病理特征、化疗敏感性和PI3K/AKT/mTOR信号通路的关系 [J ] . 疑难病杂志 , 2023 , 22 ( 1 ): 42 - 48 .

LIU H Q , ZHANG Y F , ZHANG F , et al. The relationship between serum miR-124-3p, miR-361-5p and clinicopathological characteristics, chemosensitivity and PI3K/AKT/mTOR signal pathway in patients with advanced gastric cancer [J ] . Chin J Difficult Complicat Cases , 2023 , 22 ( 1 ): 42 - 48 .

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 ] . 中华消化内镜杂志 , 2014 , 31 ( 7 ): 361 - 377 .

Digestive Endoscopy Branch of the Chinese Medical Association, Tumor Endoscopy Professional Committee of the Chinese Anti-Cancer Association . Consensus on early gastric cancer screening and endoscopic diagnosis and treatment in China (Changsha, 2014) [J ] . Chin J Dig Endosc , 2014 , 31 ( 7 ): 361 - 377 .

冯成军 , 张日光 , 韦蒙专 . 信迪利单抗联合同步放化疗对晚期宫颈癌患者肿瘤标志物及程序性死亡受体-1/程序性死亡配体1的影响 [J ] . 中华实用诊断与治疗杂志 , 2022 , 36 ( 7 ): 740 - 743 .

FENG C J , ZHANG R G , WEI M Z . Effect of sintilimab combined with synchronous radiochemotherapy on tumor markers and PD-1/PD-L1 in patients with advanced cervical cancer [J ] . J Chin Pract Diagn Ther , 2022 , 36 ( 7 ): 740 - 743 .

刘子田 , 王晓阳 , 祝新 , 等 . 白蛋白结合型紫杉醇联合奥沙利铂和替吉奥在局部不可切除的进展期胃癌转化治疗中的应用 [J ] . 中国现代普通外科进展 , 2021 , 24 ( 5 ): 374 - 377 .

LIU Z T , WANG X Y , ZHU X , et al. Application of albumin-bound paclitaxel in combination with oxaliplatin and S-1 in conversion therapy of locally unresectable advanced gastric cancer [J ] . Chin J Curr Adv Gen Surg , 2021 , 24 ( 5 ): 374 - 377 .

SHIBAMOTO M , YAMADA T , EHARA K , et al. Simultaneous presence of the hepato-spleno-mesenteric trunk, a common trunk for both inferior phrenic arteries, the left gastric artery, and a common hepatic artery that ran behind the portal vein in a patient with gastric cancer [J ] . Clin J Gastroenterol , 2022 , 15 ( 3 ): 553 - 559 .

鲍萍萍 , 吴春晓 , 顾凯 , 等 . 上海市2016年胃癌发病特征及2002年至2016年胃癌发病趋势分析 [J ] . 诊断学理论与实践 , 2022 , 21 ( 4 ): 462 - 469 .

BAO P P , WU C X , GU K , et al. Analysis on incidence of stomach cancer in 2016 and trend of incidence during 2002-2016 in Shanghai [J ] . J Diagn Concepts Pract , 2022 , 21 ( 4 ): 462 - 469 .

颜玲玲 , 吴坚芬 , 顾彬彬 , 等 . 血小板与淋巴细胞比值和中性粒细胞与淋巴细胞比值对早期胃癌诊断的预测价值 [J ] . 中华消化杂志 , 2022 , 42 ( 3 ): 163 - 170 .

YAN L L , WU J F , GU B B , et al. The predictive value of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in the diagnosis of early gastric cancer [J ] . Chin J Dig , 2022 , 42 ( 3 ): 163 - 170 .

彭晓 , 李敢春 , 陈诚 . 血管生成相关因子评估贝伐单抗一线治疗老年转移性结直肠癌预后的潜在价值 [J ] . 东南大学学报(医学版) , 2022 , 41 ( 3 ): 332 - 339 .

PENG X , LI G C , CHEN C . Potential value of serum angiogenesis-related factors as prognostic markers of first-line antiangiogenic therapy in elderly patients with metastatic colorectal cancer [J ] . J Southeast Univ Med Sci Ed , 2022 , 41 ( 3 ): 332 - 339 .

徐梓宁 , 黄敬君 , 周娟 , 等 . 程序性死亡受体-1单抗在肝动脉化疗栓塞联合分子靶向药物治疗后进展期肝细胞癌的疗效分析 [J ] . 中华内科杂志 , 2021 , 60 ( 7 ): 630 - 636 .

XU Z N , HUANG J J , ZHOU J , et al. Efficacy and safety of anti-PD-1 monoclonal antibody in advanced hepatocellular carcinoma after TACE combined with TKI therapy [J ] . Chin J Intern Med , 2021 , 60 ( 7 ): 630 - 636 .

杨敏伟 , 曾冬香 , 杨全良 , 等 . 信迪利单抗在晚期非小细胞肺癌化疗患者中的应用及对其血清细胞因子、免疫功能的影响 [J ] . 中国临床药理学杂志 , 2022 , 38 ( 24 ): 2931 - 2935 .

YANG M W , ZENG D X , YANG Q L , et al. Application of sintilimab in chemotherapy patients with advanced non-small cell lung cancer and its effect on serum cytokines and immune function [J ] . Chin J Clin Pharmacol , 2022 , 38 ( 24 ): 2931 - 2935 .

郑纪红 , 韩强 , 冯金月 , 等 . 既往胸部放疗对信迪利单抗联合多西他赛治疗Ⅳ期非小细胞肺癌病人预后的影响分析 [J ] . 安徽医药 , 2022 , 26 ( 9 ): 1865 - 1869 .

ZHENG J H , HAN Q , FENG J Y , et al. Effect of previous thoracic radiotherapy on the prognosis of patients with stage Ⅳ non-small cell lung cancer treated with sentilimab combined with docetaxel [J ] . Anhui Med Pharm J , 2022 , 26 ( 9 ): 1865 - 1869 .

刘强 , 孙少明 , 王文俊 . miR-101-3p在胃癌中的表达及其靶向 STC -1基因调控PI3K/AKT信号通路对癌细胞侵袭转移和血管生成的影响 [J ] . 肿瘤防治研究 , 2022 , 49 ( 12 ): 1223 - 1231 .

LIU Q , SUN S M , WANG W J . Expression of miR-101-3p in gastric cancer and its effects on invasion, metastasis, and angiogenesis of gastric cancer cells by targeting STC -1 gene to regulate PI3K/AKT signaling pathway [J ] . Cancer Res Prev Treat , 2022 , 49 ( 12 ): 1223 - 1231 .

张科 , 成翠娥 , 陆志平 , 等 . TGM2、NEAT1、miRNA-17-5p在胃癌组织中的表达及与疾病演进的相关性 [J ] . 河北医药 , 2022 , 44 ( 7 ): 1000 - 1004 .

ZHANG K , CHENG C E , LU Z P , et al. Expressions of TGM2, NEAT1 and miRNA-17-5p in gastric cancer tissue and their correlation with disease progression [J ] . Hebei Med J , 2022 , 44 ( 7 ): 1000 - 1004 .

吴维宇 , 汪力 , 张雪莲 , 等 . 胃癌患者血清miR-515-3p水平与临床病理特征及预后的关系 [J ] . 国际消化病杂志 , 2021 , 41 ( 2 ): 113 - 117 .

WU W Y , WANG L , ZHANG X L , et al. Relationship between serum miR-515-3p level and clinicopathological characteristics and prognosis in patients with gastric cancer [J ] . Int J Dig Dis , 2021 , 41 ( 2 ): 113 - 117 .

雷阿明 , 祝平安 , 符丽梅 , 等 . LncRNA HOTAIR通过靶基因miR-20a-5p调控淋巴瘤细胞增殖、侵袭、迁移的分子机制研究 [J ] . 中国实验血液学杂志 , 2023 , 31 ( 1 ): 89 - 95 .

LEI A M , ZHU P A , FU L M , et al. The molecular mechanism of lncRNA HOTAIR regulating the proliferation, invasion and migration of lymphoma cells through target gene miR-20a-5p [J ] . J Exp Hematol , 2023 , 31 ( 1 ): 89 - 95 . DOI: 10.19746/j.cnki.issn.1009-2137.2023.01.014 http://doi.org/10.19746/j.cnki.issn.1009-2137.2023.01.014

浏览量

1683

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

胃癌伴神经内分泌肿瘤与单纯型胃癌的免疫微环境特征比较研究

口服营养补充对胃癌根治术后存在营养风险的老年出院患者影响的前瞻性研究

胃癌领域抗肿瘤药物相关间质性肺病/肺炎的研究进展及展望

基于血清蛋白质组学的TAGLN2、CTSD等5种早期胃癌生物标志物的发现及初步验证

人工智能在胃癌诊疗和患者预后预测中的应用现状及未来展望