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Jun Wu1, Yang Guo2, Zhi-Fan Zuo3

  • 1China Medical University, The General Hospital of Northern Theater Command Training Base for Graduate, Shenyang 110016, Liaoning Province, China.

World Journal of Gastroenterology
|June 5, 2023
PubMed
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Matrix metalloproteinase-14 (MMP14) is identified as a key diagnostic gene for intrahepatic cholangiocarcinoma (ICC). This finding offers new avenues for ICC diagnosis and therapeutic target identification by understanding its role in immune cell infiltration.

Area of Science:

  • Oncology
  • Genomics
  • Immunology

Background:

  • Intrahepatic cholangiocarcinoma (ICC) is a challenging hepatobiliary malignancy characterized by late diagnosis, aggressive progression, and poor patient outcomes.
  • Identifying specific biomarkers is crucial for improving ICC diagnosis and treatment strategies.

Purpose of the Study:

  • To identify novel disease characteristic genes for intrahepatic cholangiocarcinoma (ICC) diagnosis.
  • To investigate the influence of these characteristic genes on immune cell infiltration within the ICC tumor microenvironment.

Main Methods:

  • Utilized machine learning algorithms (LASSO, SVM-RFE, RF) on gene expression datasets (GSE26566, GSE32958) to screen for ICC characteristic genes.
  • Validated diagnostic accuracy using independent datasets (GSE107943, TCGA) and Receiver Operating Characteristic (ROC) curve analysis.
Keywords:
Characteristic geneDiagnostic markersImmune infiltrationIntrahepatic cholangiocarcinomaMMP14Machine learning

Related Experiment Videos

  • Assessed immune cell infiltration patterns using CIBERSORT and ssGSEA algorithms and analyzed protein expression via the Human Protein Atlas (HPA).

    • Main Results:

    • Identified Matrix metalloproteinase-14 (MMP14) as a significant characteristic gene for ICC through integrated analysis of three machine learning algorithms.
    • MMP14 demonstrated high diagnostic accuracy in both training and validation cohorts (AUCs ranging from 0.960 to 0.999).
    • MMP14 was found to influence the infiltration of various immune cells, including monocytes and CD4 T cells, and correlate with immune checkpoint molecules.

    Conclusions:

    • Matrix metalloproteinase-14 (MMP14) serves as a valuable disease characteristic gene for intrahepatic cholangiocarcinoma (ICC).
    • MMP14 plays a role in modulating the immune cell distribution within the ICC tumor microenvironment.
    • This discovery provides a potential new diagnostic marker and therapeutic target for ICC.