河北医科大学学报 ›› 2025, Vol. 46 ›› Issue (7): 762-768.doi: 10.3969/j.issn.1007-3205.2025.07.004

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ACVRL1基因多态性与结直肠癌贝伐单抗靶向治疗反应的关系探讨

  

  1. 1.河北北方学院附属第一医院肿瘤内科，河北 张家口 075000；2.陆军第八十一集团军医院肿瘤内科，河北 张家口 075000

  • 出版日期:2025-07-25 发布日期:2025-07-24
  • 作者简介:翟明慧（1985-），女，河北衡水人，河北北方学院附属第一医院主治医师，医学硕士，从事恶性肿瘤诊治研究。

  • 基金资助:
    河北省医学科学研究课题计划（20210617）；张家口市市级科技计划项目（2021037D）

Exploration of the relationship between ACVRL1 gene polymorphism and response to bevacizumab targeted therapy in colorectal cancer

  1. 1.Department of Medical Oncology, the First Affiliated Hospital of Hebei North University, 
    Zhangjiakou 075000, China; 2.Department of Medical Oncology, Hospital of the 
    81st Group Army of the PLA, Hebei Province, Zhangjiakou 075000, China

  • Online:2025-07-25 Published:2025-07-24

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摘要： 目的 探讨类激活素受体1型（activin A receptor like type 1，ACVRL1）基因多态性与结直肠癌贝伐单抗靶向治疗反应的关系。
方法 选取2022年1月—2024年4月河北北方学院附属第一医院收治的结直肠癌患者254例，均实施贝伐单抗靶向治疗。治疗前采取外周血应用连接酶检测反应技术检测ACVRL1 rs706819、rs2293094、rs1169953位点基因多态性，并进行连锁不平衡分析；根据治疗反应将患者分为有效组和无效组，比较2组一般资料和ACVRL1 rs706819、rs2293094、rs1169953位点基因型分布与等位基因频率；Logistic回归分析确定患者治疗效果的影响因素。实时荧光定量聚合酶链反应检测不同ACVRL1基因单体型患者的癌组织ACVRL1基因表达情况。
结果 无效组ACVRL1基因rs2293094位点AA基因型与A等位基因、ACVRL1基因rs1169953位点TT基因型与T等位基因占比均高于有效组（45.10% vs. 21.18%，62.75% vs. 45.07%，52.94% vs. 26.60%，69.61% vs. 50.25%，P＜0.05）；ACVRL1 rs706819、rs2293094、rs1169953位点存在连锁不平衡，且分为4个单体型；患者贝伐单抗靶向治疗无效率为20.08%；Logistic回归分析结果显示，临床分期Ⅳ期、未低分化、ACVRL1基因H1单体型均是贝伐单抗靶向治疗效果的危险因素（P＜0.05），ACVRL1基因H2单体型、联合同步放化疗是其保护因素（P＜0.05）。ACVRL1H1单体型患者ACVRL1基因表达低于其他3种单体型（P＜0.05），H2单体型患者ACVRL1基因表达高于H3和H4单体型（P＜0.05）。
结论 ACVRL1基因H1单体型、临床分期Ⅳ期、未低分化均是结直肠癌患者靶向治疗效果的危险因素，ACVRL1基因H2单体型、联合同步放化疗则是其保护因素。


关键词: 结直肠肿瘤, 贝伐单抗, 类激活素受体1型, 基因多态性

Abstract: Objective To explore the relationship between the activin A receptor like type 1 (ACVRL1) gene polymorphism and the response to bevacizumab targeted therapy in colorectal cancer (CRC). 
Methods In total, 254 CRC patients admitted to the First Affiliated Hospital of Hebei North University from January 2022 to April 2024 were enrolled and given bevacizumab targeted therapy. Before treatment, peripheral blood was collected, ligase detection reaction technology was used to detect gene polymorphisms of the ACVRL1 rs706819, rs2293094, and rs1169953 loci, and a chain imbalance analysis was conducted. According to the treatment response, patients were divided into effective group and ineffective group. The general information and genotype distributions and allele frequencies of ACVRL1 rs706819, rs2293094, rs1169953 loci were compared between the two groups, and Logistic regression analysis was used to explore the influencing factors of ineffective treatment in patients. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect and compare the expressions of ACVRL1 gene in cancer tissues of patients with different ACVRL1 gene haplotypes. 
Results The proportions of AA genotype and A allele at the rs2293094 locus of the ACVRL1 gene and the proportions of TT genotype and T allele at the rs1169953 locus of the ACVRL1 gene in the ineffective group were higher than those in the effective group (45.10% vs. 21.18%, 62.75% vs. 45.07%, 52.94% vs. 26.60%, 69.61% vs. 50.25%, P＜0.05). There was chain imbalance in ACVRL1 rs706819, rs2293094, and rs1169953 loci, and the patients were classified into four haplotypes. The ineffective rate of bevacizumab targeted therapy in patients was 20.08%. The results of Logistic regression analysis showed that stage Ⅳ, undifferentiated status, and ACVRL1 gene H1 haplotype were all risk factors for efficacy bevacizumab targeted therapy (P＜0.05), while ACVRL1 gene H2 haplotype and combined synchronous radiotherapy and chemotherapy were protective factors (P＜0.05). The expression of ACVRL1 gene in ACVRL1H1 haplotype patients was lower than those in the other three haplotypes (P＜0.05), and the expression of ACVRL1 gene in H2 haplotype patients was higher than those in H3 and H4 haplotypes (P＜0.05). 
Conclusion The H1 haplotype, stage Ⅳ, and undifferentiated status of the ACVRL1 gene are risk factors for efficacy targeted therapy in CRC patients, while the H2 haplotype of the ACVRL1 gene and combined synchronous radiotherapy and chemotherapy are protective factors. 


Key words: colorectal neoplasms, bevacizumab, activin A receptor like type 1, gene polymorphism

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