Plasma POSTN Derived From Bile Proteome Is a Promising Biomarker for Cholangiocarcinoma With Efficacy Comparable and Complementary to CA19.9

Background: Cholangiocarcinoma presents a global health challenge due to its increasing incidence and poor prognosis, primarily resulting from delayed diagnosis. There is an urgent need for a reliable biomarker to enhance early detection. Materials and Methods: Patients with cholangiocarcinoma were enrolled into three cohorts: a discovery set (n = 6), a verification set (n = 34), and a validation set (n = 146), for seeking potential biomarkers, while patients with gallstones served as controls. Three cholangiocarcinoma transcriptome datasets from the gene expression omnibus (GEO) were analyzed. Techniques employed included liquid chromatography-tandem mass spectrometry (LC-MS/MS), multiple reaction monitoring, and enzyme-linked immunosorbent assay. Results: Using a discovery set, bile proteome profiling identified 57 upregulated proteins that were either unique to cholangiocarcinoma or exhibited ≥ 2-fold changes compared to controls. The GEO transcriptome datasets yielded 48 upregulated genes consistently expressed in cholangiocarcinoma. POSTN (periostin) emerged as a viable biomarker by intersecting these two omics analyses. In the verification set, bile and plasma POSTN levels in cholangiocarcinoma were 4.7-fold and 2.1-fold higher, respectively, compared to controls. In the validation set, the sensitivity, specificity, and AUC of plasma POSTN for diagnosing cholangiocarcinoma were 78%, 85%, and 0.86, respectively, compared to 67%, 90%, and 0.86 for CA19.9. The combination of plasma POSTN and CA19.9 improved these metrics to 87%, 91%, and 0.94, respectively. Protein interactome analysis demonstrated that POSTN was predominantly connected to structural proteins of extracellular matrix (ECM). Patients with higher plasma POSTN levels exhibited higher expression of transcriptional regulators of epithelia-mesenchymal transition (EMT) and worse overall survival compared with those with lower levels. Conclusions: Plasma POSTN, derived from the bile proteome, demonstrates both comparable and complementary efficacy to CA19.9, emerging as a promising biomarker for diagnosing cholangiocarcinoma. Beyond its diagnostic capability, POSTN's role in extracellular matrix interactions and EMT regulation highlights its prognostic potential.