Discovery and Qualification of Serum Protein Biomarker Candidates for Cholangiocarcinoma Diagnosis

Abstract

Cholangiocarcinoma (CCA) is a major health problem in northeastern Thailand. The majority of CCA cases are clinically silent and difficult to detect at an early stage. Although abdominal ultrasonography (US) can detect premalignant periductal fibrosis (PDF), this method is not suitable for screening populations in remote areas. With the goal of developing a blood test for detecting CCA in the at-risk population, we carried out serum protein biomarker discovery and qualification. Label-free shotgun proteomics was performed on depleted serum samples from 30 participants (n = 10 for US-normal, US-PDF, and CCA groups). Of 40 protein candidates selected using multiple reaction monitoring on 90 additional serum samples (n = 30 per group), 11 discriminatory proteins were obtained using supervised multivariate statistical analysis. We further evaluated 3 candidates using ELISA and immunohistochemistry (IHC). S100A9, thioredoxin (TRX), and cadherin-related family member 2 (CDHR2) were significantly different between CCA and normal, and CCA and PDF groups when measured in an additional 247 serum samples (P < 0.0001). By IHC, TRX and CDHR2 were detected in the cytoplasm and nucleus of CCA and inflammatory cells. S100A9 was detected in the infiltrating tumor stroma immune cells. Proteomics discovery and qualification in depleted sera revealed promising biomarker candidates for CCA diagnosis.

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

“…The protein models demonstrated vital role for predicting prognosis, which including bladder cancer, esophageal squamous cell carcinoma and pancreatic ductal adenocarcinoma [25][26][27]. Abnormal expression of various protein biomarkers in cancer cells or inflammatory cells demonstrated prediction potential in cancers [21,28,29]. And a prediction model would demonstrate much better specificity and sensitivity than one biomarker.…”

Urinary proteome profiling for stratifying patients with familial Parkinson’s disease

“…Importantly, urine contains not only kidney and urinary tract proteins but also filtered plasma proteins originating from distal organs, including the brain (Decramer et al, 2008;An & Gao, 2015). Therefore, urine protein analysis may provide diagnostic and prognostic opportunities for both urogenital and non-renal diseases (Kaiser et al, 2004;Mischak et al, 2004;Nguyen et al, 2005;Tantipaiboonwong et al, 2005;Adachi et al, 2006;Ward et al, 2008;Zimmerli et al, 2008;Kentsis et al, 2009;Nagaraj & Mann, 2011;Kentsis et al, 2013;Metzger et al, 2013;Duangkumpha et al, 2019;Ferrari et al, 2019). Recent technical advances in fast and high-throughput sample preparation methods in conjunction with improvements in high-accuracy mass spectrometry (MS)-based proteomics have enabled characterization of the urinary proteome (Berger et al, 2015;Batth et al, 2019;Ding et al, 2020).…”

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

“…To date, proteomics studies have been used to analyze the pattern of all proteins in a patient's sera of many types of cancer [12][13][14]. Recent results of Duangkumpha et al that studied the candidate proteins in sera of CCA patients compared to normal groups by mass spectrophotometry found statistically increasing levels of S100 calcium-binding protein A9 (S100A9) that had the potential to be used as the diagnostic biomarker of CCA patients [15]. A meta-analysis revealed that the detection of mucin 5AC (MUC5AC) in sera could be used as a powerful biomarker of CCA by providing a specificity of up to 97% and sensitivity of 63% [16][17][18].…”