Proteomics and Metabolomics for the Identification of Early Diagnostic Biomarkers in a Hamster Model of Cholangiocarcinoma
Kanyarat Boonprasert
Graduate Studies, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathumthani, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, Thailand.
Wanna Chaijaroenkul
Graduate Studies, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathumthani, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, Thailand.
Tullayakorn Plengsuriyakarn
Graduate Studies, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathumthani, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, Thailand.
Kesara Na-Bangchang *
Graduate Studies, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathumthani, Thailand and Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, Thailand.
*Author to whom correspondence should be addressed.
Abstract
Background: Cholangiocarcinoma (CCA) poses a significant public health challenge, particularly in northeastern Thailand, which reports the highest prevalence worldwide. Early detection and effective intervention remain difficult due to the lack of sensitive and specific biomarkers. Recent advances in proteomics and metabolomics have created new opportunities for biomarker discovery in CCA.
Aim: This study aimed to identify novel plasma proteins and metabolites as potential biomarkers for the early diagnosis of CCA.
Methods: Six-week-old male and female Syrian hamsters (100-120 g) were housed under standard environmental conditions (22 ± 3 °C, 30-70% relative humidity, 12-h light-dark cycle) with free access to standard food and water ad libitum. Plasma samples were obtained from hamsters with Opisthorchis viverrini (OV) and dimethylnitrosamine (DMN)-induced CCA, as well as from healthy controls (n=3 per group). The samples were analysed using LC-MS/MS-based proteomics and metabolomics. Fold-change analysis was conducted to quantify the differential expression of identified proteins between the CCA and control groups, with statistical significance defined as p≤0.05.
Results: Proteomic profiling identified over 5,000 proteins, of which 572 were uniquely expressed in CCA-induced hamsters at week 12. Fold-change analysis revealed 412 and 545 upregulated proteins at weeks 8 and 12, respectively, which are functionally linked to cell proliferation, signal transduction, and metabolic regulation. Concurrently, metabolomic analysis identified 273 metabolites, of which 59 were significantly upregulated in the CCA group, including cystathionine, putrescine, UDP-N-acetylglucosamine, and flavin mononucleotide (FMN).
Conclusions: This study provides preliminary insights into candidate proteomic and metabolomic biomarkers for the early detection of CCA. These findings offer a foundational hypothesis for future research. Larger longitudinal studies, including validation in human cohorts, are warranted to confirm the clinical applicability of these novel biomarkers.
Keywords: Cholangiocarcinoma, proteomics, metabolomics, biomarkers, early diagnosis, hamster model