Plasma checkpoint protein 1 (Chk1) as a potential diagnostic biomarker for opisthorchiasis and cholangiocarcinoma

Article type: Research Article

Authors: Phanaksri, Teva^a | Yingchutrakul, Yodying^b | Roytrakul, Sittiruk^c | Prasopdee, Sattrachai^a | Kunjantarachot, Anthicha^a | Butthongkomvong, Kritiya^d | Tesana, Smarn^a | Sathavornmanee, Thanakrit^e | Thitapakorn, Veerachai^{a; *}

Affiliations: [a] Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected Parasitic Diseases, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand | [b] Proteomics Research Team, National Omics Center, NSTDA, Pathumthani, Thailand | [c] Proteomics Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, Pathumthani, Thailand | [d] Medical Oncology Unit, Udonthani Cancer Hospital, Ministry of Public Health, Udon Thani, Thailand | [e] Chonburi Hospital, Ministry of Public Health, Chonburi, Thailand

Correspondence: [*] Corresponding author: Veerachai Thitapakorn, Chulabhorn International College of Medicine, Thammasat university, 99 Moo 18, Phaholyothin Road, Klong Luang District, Pathumthani, 12120, Thailand. Tel.: +66 2 986 9213 ext. 4478; Fax: +66 2 986 9213 ext. 7598; E-mail: veur@staff.tu.ac.th.

Abstract: BACKGROUND: Patients infected with a parasite often develop opisthorchiasis viverrini, which often progresses into cholangiocarcinoma (CCA) due to the asymptomatic nature of the infection. Currently, there are no effective diagnostic methods for opisthorchiasis or cholangiocarcinoma. OBJECTIVE: The aim of this study was to identify the host-responsive protein that can be developed as a diagnostic biomarker of opisthorchiasis and cholangiocarcinoma. METHODS: Plasma samples were collected from non-OVCCA, OV, and CCA subjects, and the proteomes were investigated by LC-MS/MS. Venn diagrams and protein network prediction by STITCH were used to identify the potential biomarkers. The level of candidate protein, the plasma checkpoint protein 1 (Chk1), was measured by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: Chk1 was present in the center of the protein network analysis in both the OV and CCA groups. In addition, the plasma Chk1 levels were significantly increased in both groups (P< 0.05). The sensitivity of the opisthorchiasis viverrini and cholangiocarcinoma was 59.38% and 65.62%, respectively, while the specificity of both was 85.71%. CONCLUSION: Chk1 was identified by differential plasma proteomes and was increased in O. viverrini-infected and cholangiocarcinoma-derived plasma samples. Higher levels of plasma Chk1 levels may serve as a potential diagnostic biomarker for opisthorchiasis and cholangiocarcinoma.

Keywords: Opisthorchis viverrini, cholangiocarcinoma, checkpoint protein 1, plasma proteome, LC-MS/MS

DOI: 10.3233/CBM-210170

Journal: Cancer Biomarkers, vol. 33, no. 1, pp. 43-55, 2022