Bile-derived RNA N6-methyladenosine (m6A) methylation as a novel liquid biopsy biomarker for pancreatic cancer
Abstract
BackgroundPancreatic cancer (PCA) is a highly lethal malignancy with limited biomarkers for early diagnosis. Bile-derived epitranscriptomic biomarkers remain largely unexplored. We investigated whether bile-derived RNA N6-methyladenosine (m6A) methylation could serve as a diagnostic biomarker for PCA.MethodsBile samples were collected from patients with PCA (n = 7), biliary tract cancer (BTC; n = 33), and common bile duct (CBD) stones (n = 10). Pancreatic juice samples from patients with pancreatic neoplastic lesions (PNLs; n = 2) and PCA (n = 5) were analyzed as an exploratory cohort. Global RNA m6A was quantified in duplicate using an ELISA-based colorimetric assay. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis.ResultsBile-derived RNA m6A levels were higher in PCA than in the comparison groups. Bile-derived RNA m6A discriminated PCA from the combined BTC and CBD stone groups with an AUC of 0.993 (bootstrap 95% CI, 0.970–1.000). The exploratory cut-off of 5.50% yielded 100.0% sensitivity and 97.7% specificity. In the exploratory pancreatic juice cohort, the AUC was 0.600 (bootstrap 95% CI, 0.200–1.000), with a 4.16% cut-off, 60.0% sensitivity, and 100.0% specificity.ConclusionBile-derived global RNA m6A methylation was associated with PCA in this proof-of-concept cohort. The diagnostic performance and data-derived cut-off are preliminary and require validation in larger prospective independent multicenter cohorts before clinical application.
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BibTeX
@article{han2026bilederived,
title = {{Bile-derived RNA N6-methyladenosine (m6A) methylation as a novel liquid biopsy biomarker for pancreatic cancer}},
author = {Jin-Yi Han and Keun Soo Ahn and Min Jae Kim and In Soo Cho and Tae-Seok Kim and Yong Hoon Kim and Kyung In Shin and Kwang Bum Cho},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1955611},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1955611},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bile-derived RNA N6-methyladenosine (m6A) methylation as a novel liquid biopsy biomarker for pancreatic cancer
AU - Jin-Yi Han
AU - Keun Soo Ahn
AU - Min Jae Kim
AU - In Soo Cho
AU - Tae-Seok Kim
AU - Yong Hoon Kim
AU - Kyung In Shin
AU - Kwang Bum Cho
PY - 2026
DA - 2026/11/03
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1955611
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1955611
AB - BackgroundPancreatic cancer (PCA) is a highly lethal malignancy with limited biomarkers for early diagnosis. Bile-derived epitranscriptomic biomarkers remain largely unexplored. We investigated whether bile-derived RNA N6-methyladenosine (m6A) methylation could serve as a diagnostic biomarker for PCA.MethodsBile samples were collected from patients with PCA (n = 7), biliary tract cancer (BTC; n = 33), and common bile duct (CBD) stones (n = 10). Pancreatic juice samples from patients with pancreatic neoplastic lesions (PNLs; n = 2) and PCA (n = 5) were analyzed as an exploratory cohort. Global RNA m6A was quantified in duplicate using an ELISA-based colorimetric assay. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis.ResultsBile-derived RNA m6A levels were higher in PCA than in the comparison groups. Bile-derived RNA m6A discriminated PCA from the combined BTC and CBD stone groups with an AUC of 0.993 (bootstrap 95% CI, 0.970–1.000). The exploratory cut-off of 5.50% yielded 100.0% sensitivity and 97.7% specificity. In the exploratory pancreatic juice cohort, the AUC was 0.600 (bootstrap 95% CI, 0.200–1.000), with a 4.16% cut-off, 60.0% sensitivity, and 100.0% specificity.ConclusionBile-derived global RNA m6A methylation was associated with PCA in this proof-of-concept cohort. The diagnostic performance and data-derived cut-off are preliminary and require validation in larger prospective independent multicenter cohorts before clinical application.
SN - 2234-943X
ER -