Serum proteomic profiling identifies pathways and protein signatures associated with early versus late recurrence in cholangiocarcinoma.
6 affiliations
- 1Cholangiocarcinoma Research Institute, Khon Kaen University Khon Kaen 40002 Thailand [email protected] [email protected].
- 2Department of Surgery, Faculty of Medicine, Khon Kaen University Khon Kaen 40002 Thailand.
- 3Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University Khon Kaen 40002 Thailand.
- 4Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University Khon Kaen 40002 Thailand.
- 5Department of Pathology, Faculty of Medicine, Khon Kaen University Khon Kaen 40002 Thailand.
- 6Proteomics Research Laboratory, Genome Institute, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency Pathum Thani 120120 Thailand.
Abstract
Cholangiocarcinoma (CCA) is characterized by frequent postoperative recurrence, yet reliable biomarkers for distinguishing early from late recurrence remain limited. This study aimed to identify serum protein biomarkers associated with early versus late recurrence and develop a proteomic recurrence score (PRS) to distinguish these recurrence groups after curative resection. Serum proteomic profiling was performed using LC-MS/MS in patients with resected CCA. Candidate proteins were identified through integrated univariate and multivariate analyses, followed by pathway enrichment and protein-protein interaction analyses. Proteins with ≥50% detection frequency were refined for model development, and elastic net - based feature selection within a repeated nested cross-validation framework was used to derive the proteins for construction of the PRS. A total of 232 candidate proteins associated with recurrence were identified, highlighting enrichment of immune/inflammatory signaling, metabolic reprogramming, and tumor progression pathways. Refinement yielded 33 consistently detectable proteins. During nested model-size optimization, the 20-protein candidate model achieved a patient-level OOF ROC-AUC of 0.937 (95% CI, 0.881-0.979). Based on feature-selection stability, the 20 most stable proteins were subsequently prioritized as a fixed exploratory signature for PRS construction, achieving a patient-level OOF ROC-AUC of 0.948 (95% CI, 0.895-0.988). A PRS derived from an exploratory 20-protein signature was significantly associated with clinicopathological variables and independently associated overall survival in multivariable Cox regression. Comprehensive serum proteomic profiling identified biological pathways associated with recurrence timing and enabled the prioritization of an exploratory 20-protein PRS for distinguishing early from late recurrence among patients with CCA. The PRS demonstrated promising internal discrimination and was independently associated with overall survival. External validation in independent cohorts is required before clinical application.
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BibTeX
@article{prajumwongs2026serum,
title = {{Serum proteomic profiling identifies pathways and protein signatures associated with early versus late recurrence in cholangiocarcinoma.}},
author = {Piya Prajumwongs and Attapol Titapun and Vasin Thanasukarn and Apiwat Jareanrat and Natcha Khuntikeo and Nisana Namwata and Poramate Klanrit and Arporn Wangwiwatsin and Jarin Chindaprasirt and Prakasit Sa-Ngiamwibool and Nattha Muangritdech and Sawanya Charoenlappanit and Sittiruk Roytrakul and Watcharin Loilome},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra05199e},
url = {https://europepmc.org/article/MED/42835936},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Serum proteomic profiling identifies pathways and protein signatures associated with early versus late recurrence in cholangiocarcinoma.
AU - Piya Prajumwongs
AU - Attapol Titapun
AU - Vasin Thanasukarn
AU - Apiwat Jareanrat
AU - Natcha Khuntikeo
AU - Nisana Namwata
AU - Poramate Klanrit
AU - Arporn Wangwiwatsin
AU - Jarin Chindaprasirt
AU - Prakasit Sa-Ngiamwibool
AU - Nattha Muangritdech
AU - Sawanya Charoenlappanit
AU - Sittiruk Roytrakul
AU - Watcharin Loilome
PY - 2026
DA - 2026/10/05
JO - RSC advances
DO - 10.1039/d6ra05199e
UR - https://europepmc.org/article/MED/42835936
AB - Cholangiocarcinoma (CCA) is characterized by frequent postoperative recurrence, yet reliable biomarkers for distinguishing early from late recurrence remain limited. This study aimed to identify serum protein biomarkers associated with early versus late recurrence and develop a proteomic recurrence score (PRS) to distinguish these recurrence groups after curative resection. Serum proteomic profiling was performed using LC-MS/MS in patients with resected CCA. Candidate proteins were identified through integrated univariate and multivariate analyses, followed by pathway enrichment and protein-protein interaction analyses. Proteins with ≥50% detection frequency were refined for model development, and elastic net - based feature selection within a repeated nested cross-validation framework was used to derive the proteins for construction of the PRS. A total of 232 candidate proteins associated with recurrence were identified, highlighting enrichment of immune/inflammatory signaling, metabolic reprogramming, and tumor progression pathways. Refinement yielded 33 consistently detectable proteins. During nested model-size optimization, the 20-protein candidate model achieved a patient-level OOF ROC-AUC of 0.937 (95% CI, 0.881-0.979). Based on feature-selection stability, the 20 most stable proteins were subsequently prioritized as a fixed exploratory signature for PRS construction, achieving a patient-level OOF ROC-AUC of 0.948 (95% CI, 0.895-0.988). A PRS derived from an exploratory 20-protein signature was significantly associated with clinicopathological variables and independently associated overall survival in multivariable Cox regression. Comprehensive serum proteomic profiling identified biological pathways associated with recurrence timing and enabled the prioritization of an exploratory 20-protein PRS for distinguishing early from late recurrence among patients with CCA. The PRS demonstrated promising internal discrimination and was independently associated with overall survival. External validation in independent cohorts is required before clinical application.
SN - 2046-2069
ER -