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Publications

Journal Article Ppublish

PubMed: 40697243 DOI: 10.4251/wjgo.v17.i7.108455

Genetic evidence for the causal influence of inflammatory factors on intrahepatic cholangiocarcinoma risk.

World J Gastrointest Oncol 17(7):108455

Authors: Bing Chen, Jun Chen, Zhi-Tao Chen, Zhang-Peng Feng, Han-Bei Lv, Guo-Ping Jiang

Affiliations

  • School of Medicine, Zhejiang Chinese Medical University, Hangzhou 310022, Zhejiang Province, China.
  • Department of General Surgery, The Second People's Hospital of Guizhou Province, Hangzhou 310022, Zhejiang Province, China.
  • Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310022, Zhejiang Province, China.
  • Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310022, Zhejiang Province, China.

Abstract

BACKGROUND

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver cancer subtype with limited effective treatment options. Emerging evidence suggests that inflammatory factors play a critical role in ICC progression within the tumor microenvironment (TME). However, causal relationships between specific inflammatory factors and ICC risk remain unclear.

AIM

To investigate the causal relationship between inflammatory factors and ICC.

METHODS

This study used Mendelian randomization (MR) and Bayesian weighted MR (BWMR) analyses to investigate the causal impact of inflammatory factors on ICC risk. Genetic data from genome-wide association studies were utilized to identify and validate instrumental variables for 91 inflammatory factors, followed by sensitivity analyses to ensure robustness.

RESULTS

MR analysis identified significant associations between elevated levels of artemin and matrix metalloproteinase (MMP)-10 and increased ICC risk. BWMR and meta-MR analysis results validated these associations. Sensitivity analyses confirmed the stability of these findings, indicating that specific inflammatory factors may contribute causally to ICC development.

CONCLUSION

This study provides evidence that certain inflammatory factors, particularly artemin and MMP-10, are causally linked to ICC risk, identifying them as potential risk factors and therapeutic targeting. These findings enhance the understanding of the inflammatory components of the TME in ICC, supporting the development of targeted intervention strategies.

MeSH

Neoplasms, Matrix Metalloproteinases, Therapeutics, Cholangiocarcinoma, Intrahepatic Cholangiocarcinoma