Journal of Hebei Medical University ›› 2025, Vol. 46 ›› Issue (7): 762-768.doi: 10.3969/j.issn.1007-3205.2025.07.004

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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

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