Establishment of a Potential Serum Biomarker Panel for the Diagnosis and Prognosis of Cholangiocarcinoma Using Decision Tree Algorithms.

Phongsaran Kimawaha,Narong Khuntikeo,Apinya Jusakul,Anchalee Techasen,Prem Junsawang,Raynoo Thanan,Attapol Titapun

doi:10.3390/diagnostics11040589

Phongsaran Kimawaha, Narong Khuntikeo + Show 5 more

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https://doi.org/10.3390/diagnostics11040589

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Journal: Diagnostics	Publication Date: Mar 25, 2021
Citations: 10	License type: CC BY 4.0

Affiliation: Khon Kaen University

Abstract

Potential biomarkers which include S100 calcium binding protein A9 (S100A9), mucin 5AC (MUC5AC), transforming growth factor β1 (TGF-β1), and angiopoietin-2 have previously been shown to be effective for cholangiocarcinoma (CCA) diagnosis. This study attempted to measure the sera levels of these biomarkers compared with carbohydrate antigen 19-9 (CA19-9). A total of 40 serum cases of CCA, gastrointestinal cancers (non-CCA), and healthy subjects were examined by using an enzyme-linked immunosorbent assay. The panel of biomarkers was evaluated for their accuracy in diagnosing CCA and subsequently used as inputs to construct the decision tree (DT) model as a basis for binary classification. The findings showed that serum levels of S100A9, MUC5AC, and TGF-β1 were dramatically enhanced in CCA patients. In addition, 95% sensitivity and 90% specificity for CCA differentiation from healthy cases, and 70% sensitivity and 83% specificity for CCA versus non-CCA cases was obtained by a panel incorporating all five candidate biomarkers. In CCA patients with low CA19-9 levels, S100A9 might well be a complementary marker for improved diagnostic accuracy. The high levels of TGF-β1 and angiopoietin-2 were both associated with severe tumor stages and metastasis, indicating that they could be used as a reliable prognostic biomarkers panel for CCA patients. Furthermore, the outcome of the CCA burden from the Classification and Regression Tree (CART) algorithm using serial CA19-9 and S100A9 showed high diagnostic efficiency. In conclusion, results have shown the efficacy of CCA diagnosis and prognosis of the novel CCA-biomarkers panel examined herein, which may prove be useful in clinical settings.

Highlights

Cholangiocarcinoma (CCA) is a complex group of malignancies that have arisen in the biliary tree
Serum levels of S100 calcium binding protein A9 (S100A9), mucin 5AC (MUC5AC), transforming growth factor β1 (TGF-β1), angiopoietin-2, and carbohydrate antigen 19-9 (CA19-9) were examined in 40 patients diagnosed with CCA, 40 non-CCA subjects, and 40 healthy individuals
The present study suggested the efficacy of utilizing combined biomarker analysis for CCA diagnosis

Summary

Introduction

Cholangiocarcinoma (CCA) is a complex group of malignancies that have arisen in the biliary tree. It is the most common liver cancer and the major public health issue of the northeastern region in Thailand [1,2]. Infection with the liver fluke Opisthorchis viverrini, which causes chronic inflammation and advanced periductal fibrosis, is a significant oncogenic risk factor for CCA development in this region. The critical challenge related to this cancer is effective diagnosis and prognosis because CCA is typically asymptomatic in early stages, most often diagnosed in late stages, and difficult to differentiate from other gastrointestinal cancers (GI) including hepatocellular carcinoma (HCC) [3,4]. The blood-based tumor biomarker, carbohydrate antigen 19-9 (CA19-9), is generally used to diagnose CCA. The CA19-9 marker provides unsatisfactory sensitivity and specificity values because 7% of individuals in the population are Lewis antigen-negative with no or low production of CA19-9, and this marker is often elevated in benign and other GI tract malignancies [5,6]

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