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Comparative transcriptomic analysis uncovers molecular heterogeneity in hepatobiliary cancers.
Nabanita Roy1, Ria Lodh1, Susmita Mandal2
1Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Sonitpur, Assam, 784028, India.
Translational Oncology
|November 15, 2024
Summary
This study identified unique transcriptomic signatures in hepatobiliary cancers (HBCs), revealing distinct molecular pathways and potential therapeutic targets for gallbladder cancer (GBC), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (ICC). Findings pave the way for personalized treatments.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Hepatobiliary cancers (HBCs) present a significant global health burden with limited targeted biomarkers.
- Gallbladder cancer (GBC), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (ICC) often receive generalized treatments due to shared risk factors and anatomical complexities.
Purpose of the Study:
- To identify specific transcriptomic signatures differentiating GBC, HCC, and ICC.
- To explore the molecular heterogeneity and identify potential therapeutic targets within these distinct hepatobiliary cancers.
Main Methods:
- Transcriptomic data analysis to reveal distinct expression profiles and functional annotations.
- Gene co-expression network (GCN) and protein-protein interaction (PPI) network analyses to identify key genes.
- Epithelial-Mesenchymal Transition (EMT) score analysis and external validation using The Cancer Genome Atlas (TCGA).
Main Results:
- Distinct transcriptomic profiles and associated biological pathways were identified for GBC (cell cycle), HCC (immune modulation), and ICC (lipid metabolism).
- Key candidate genes (e.g., MAPK3, ERBB2, AC069287.1, ACTN2, TRPC1, BACE1) and conserved FOX family transcription factors were pinpointed.
- EMT analysis showed varied phenotypic characteristics, with stronger EMT correlations for TFs in GBC and ICC compared to HCC.
Conclusions:
- Hepatobiliary cancers exhibit significant molecular heterogeneity, necessitating tailored therapeutic strategies.
- Identified transcriptomic signatures and key genes offer potential for developing novel, personalized therapeutic interventions for GBC, HCC, and ICC.
- The study highlights the importance of understanding cancer-specific molecular profiles for advancing precision oncology in hepatobiliary malignancies.
