Discovery of Serotransferrin Glycoforms: Novel Markers for Diagnosis of Liver Periductal Fibrosis and Prediction of Cholangiocarcinoma.

Wassana Jamnongkan,Chawalit Pairojkul,Mariana Barboza,Nittaya Chamadol,Narong Khuntikeo,Paiboon Sithithaworn,Puangrat Yongvanit,Anchalee Techasen,Raynoo Thanan,Carlito B Lebrilla,Watcharin Loilome

doi:10.3390/biom9100538

Wassana Jamnongkan, Chawalit Pairojkul + Show 9 more

Open Access

https://doi.org/10.3390/biom9100538

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Abstract

Cholangiocarcinoma (CCA) caused by chronic liver fluke infection is a major public health problem in Northeast Thailand. Identification of CCA risk groups is urgently needed for the control of CCA in this region. Periductal fibrosis (PDF) induced by chronic inflammation of bile ducts is known as a pre-neoplastic lesion of CCA. We aimed to identify the serum CCA and PDF biomarkers using mass spectrometry (UPLC-ESI-QqQ) with multiple reaction mode (MRM) analysis. Here, serum levels of serotransferrin glycoforms at the glycopeptide level were measured in the sera of CCA (n = 100), PDF (n = 50), and healthy control (n = 100) subjects. The results indicated that serotransferrin peptide levels were generally the same between the control and PDF groups, whereas CCA patients had reduced levels. Moreover, 56 serotransferrin glycoforms were detected, with nine increased in CCA compared to control subjects. Among them, the serum levels of four glycoforms were increased in PDF and CCA patients compared to control subjects. In particular, highly sialylated multi-branched glycans of serotransferrin serum were significantly correlated with poor prognosis and tumor stage in CCA patients. Taken together, these glycoforms could be used as risk biomarkers and prognosis and diagnosis markers of CCA.

Highlights

Cholangiocarcinoma (CCA) is a slowly progressing tumor, in which patients develop symptoms over a long period of time
The areas under the receiver operating characteristic (ROC) curves (AUC) (Figure 2B,C) between the control group, the Periductal fibrosis (PDF) group, and the CCA group were 0.812 and 0.814, respectively
Our study revealed that the serotransferrin protein levels of CCA patients were significantly lower than that of the control and PDF groups

Summary

Introduction

Cholangiocarcinoma (CCA) is a slowly progressing tumor, in which patients develop symptoms over a long period of time. Because the majority of CCA cases are clinically silent and not detected in early stages of the disease, CCA is a tumor with a high mortality rate. In northeast Thailand, where CCA is highly endemic, the major cause of CCA is liver fluke (Opisthorchis viverrini (Ov)) infection [2]. This parasite infection induces periductal fibrosis (PDF), which develops into CCA in animal models [3,4]. Since CCA is a major cause of death in Thailand, earlier identification of CCA risk group is urgently needed for better control of CCA in regions where it is endemic. PDF and CCA are usually diagnosed using a combination of several advanced techniques, including abdominal ultrasonography, CT scanning, and tissue biopsy

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