Integrated Transcriptomic Analysis and Functional Validation Identify CNTN1 as a Novel Metastatic Driver in Hilar...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Hilar cholangiocarcinoma (HC) is an aggressive cancer with poor outcomes.
• Understanding HC's molecular drivers is crucial for developing effective treatments.

Purpose of the Study:

• To identify and functionally validate key genes and pathways in HC pathogenesis.
• To investigate the role of Contactin-1 (CNTN1) in HC invasion and metastasis.

Main Methods:

• RNA sequencing (RNA-seq) on paired HC tumors and adjacent tissues.
• Bioinformatic analyses including Gene Ontology (GO), KEGG, and protein-protein interaction (PPI) networks.
• In vitro Transwell assays and in vivo orthotopic metastatic models to assess CNTN1 function.

Main Results:

• 35 differentially expressed genes (DEGs) identified in HC, linked to cell adhesion and axon development.
• Six hub genes identified, including CNTN1, which was significantly upregulated in HC.
• CNTN1 promotes HC cell invasion and metastasis by activating the PI3K-AKT pathway and inducing epithelial-mesenchymal transition (EMT).

Conclusions:

• CNTN1 is a critical oncogenic driver in HC, promoting metastasis via PI3K-AKT-mediated EMT.
• CNTN1 shows potential as a prognostic biomarker and therapeutic target for HC.