Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Ann Med. 2024 Dec;56(1):2396559. doi: 10.1080/07853890.2024.2396559. Epub 2024 Sep 9.

Abstract

Introduction: Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab.

Methods: Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan-Meier method and Cox regression models.

Results: Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001-3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150-5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078-6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173-12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043).

Conclusions: Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6-VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

Keywords: Colorectal cancer; antiangiogenesis; chromosomal instability; liver metastases; prognosis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / therapeutic use
  • Chromosomal Instability*
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Female
  • Hepatectomy*
  • Humans
  • Interleukin-6 / metabolism
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / secondary
  • Liver Neoplasms* / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Bevacizumab
  • Antineoplastic Agents, Immunological
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • VEGFA protein, human

Grants and funding

This study was funded by grants from the Natural Science Foundation of Guangdong Province, China (no. 2023A1515010417), Medical Scientific Research Foundation of Guangdong Province, China (no. A2021130), and Shenzhen Science and Technology Plan Projects (no. JCYJ20220531094015034).