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

doi:10.19401/j.cnki.1007-3639.2024.05.006

摘要/Abstract

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⁺ T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（P<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（P<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（P>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。

关键词: 贝伐珠单抗, 程序性死亡蛋白-1抑制剂, 胃癌, miR-20a-5p, miR-515-3p

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 (P<0.05). After treatment, serum carbohydrate antigen 12-5 (CA12-5), carcinoembryonic antigen (CEA) and cytokerantin-19-fragment antigen 21-1 (CYFRA21-1) levels were lower in observation group than in control group (P<0.05). CD4⁺ T lymphocyte and CD4⁺/CD8⁺ T lymphocyte ratio were higher in observation group than in control group after treatment (P<0.05), and CD8⁺ T lymphocyte was lower in observation group than in control group after treatment (P<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 (P<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%) (P>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.

Key words: Bevacizumab, Programmed death-1 inhibitor, Gastric cancer, miR-20a-5p, miR-515-3p

中图分类号:

R735.2

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.

WANG Fei, LIU Pei, HU Nan. 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.

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General information	Observation group	Control group	χ²/t value	P value
Gender			0.048	0.826
Male	22 (52.38)	24 (57.14)
Female	20 (47.62)	18 (42.86)
Differentiation degree			0.254	0.614
Medium-high differentiation	33 (78.57)	30 (71.43)
Poor differentiation	9 (21.43)	12 (28.57)
TNM stage			0.051	0.822
Stage Ⅲ	17 (40.48)	15 (35.71)
Stage Ⅳ	25 (59.52)	27 (64.29)
Lymph node metastasis			0.071	0.790
Yes	8 (19.02)	10 (23.81)
No	34 (80.95)	32 (76.19)
Pathological type			0.193	0.908
Mucinous adenocarcinoma	13 (30.95)	12 (28.57)
Papillary adenocarcinoma	18 (42.86)	20 (47.62)
Adeno-squamous carcinoma	11 (26.19)	10 (23.81)
Age/year $\bar{x} \pm s$	49.62±7.66	49.52±8.16	0.058	0.954
Focal diameter/cm $\bar{x} \pm s$	4.85±1.02	4.79±1.16	0.252	0.802
BMI/(kg·m^-2) $\bar{x} \pm s$	24.62±1.35	24.88±1.41	0.863	0.391

Group	Observation group	Control group	χ²/t value	P value
CR	11 (26.19)	6 (14.29)
PR	18 (42.86)	11 (26.19)
SD	7 (16.67)	10 (23.81)
PD	6 (14.29)	15 (35.71)
ORR	29 (69.05)	17 (40.48)	6.920	0.009
DCR	36 (85.71)	27 (64.29)	5.143	0.023

Group	Case n	Observation group	Control group	t value	P value
CA12-5/(U·mL^-1)	Before treatment	68.62±5.05	69.01±5.28	0.346	0.730
	After treatment	26.11±2.85^a	48.31±4.15^a	28.578	0.000
CEA/(ng·mL^-1)	Before treatment	91.62±8.26	92.11±8.96	0.261	0.795
	After treatment	45.62±5.26^a	70.82±7.11^a	18.466	0.000
CYFRA21-1/(ng·mL^-1)	Before treatment	10.38±2.62	10.44±2.56	0.106	0.916
	After treatment	2.16±1.62^a	5.92±1.84^a	9.940	0.000

Group	Case n	Observation group	Control group	t value	P value
CD4^{+ T lymphocyte}/%	Before treatment	28.62±3.66	28.52±3.95	0.120	0.905
	After treatment	42.58±5.64^a	36.28±4.16^a	5.826	0.000
CD8^{+ T lymphocyte}/%	Before treatment	38.62±5.55	38.71±5.29	0.076	0.940
	After treatment	29.13±1.52^a	33.05±2.85^a	7.865	0.000
CD4⁺/CD8^{+ T lymphocyte ratio}	Before treatment	0.75±0.11	0.78±0.12	1.194	0.236
	After treatment	1.43±0.34^a	1.11±0.19^a	5.325	0.000

Group	Case n	Observation group	Control group	t value	P value
miR-20a-5p	Before treatment	0.71±0.13	0.74±0.15	0.979	0.330
	After treatment	0.48±0.10^a	0.55±0.12^a	2.904	0.005
miR-515-3p	Before treatment	2.41±0.34	2.45±0.29	0.580	0.563
	After treatment	1.02±0.11^a	1.68±0.13^a	25.117	0.000