Establishment and verification of potential biomarkers for cholangiocarcinoma

Wang,Shuai; Wang,Shuai; Yu,Leilei; Yu,Leilei; Sun,Xiangyu; Sun,Xiangyu; Zhang,Bo; Zhang,Bo

doi:10.3892/etm.2022.11483

Establishment and verification of potential biomarkers for cholangiocarcinoma

Authors:
- Shuai Wang
- Leilei Yu
- Xiangyu Sun
- Bo Zhang
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Affiliations: The Third Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin 300100, P.R. China, Department of Endocrinology, The Affiliated Taian City Central Hospital of Qingdao University, Tai'an, Shandong 271000, P.R. China, The Fourth Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin, 300100, P.R. China, Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China
Published online on: June 30, 2022 https://doi.org/10.3892/etm.2022.11483
Article Number: 546
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cholangiocarcinoma (CCA) is a malignancy arising from multiple locations along the biliary tree, which is still lacking effective diagnostic biomarkers. The present study aimed to provide a comprehensive differential gene expression profile for the disease. The differentially expressed genes (DEGs) for CCA were explored in‑depth using a Gene Expression Omnibus (GEO) dataset, an internal cohort of clinical participants as well as in vitro experiments with the HUCCT1 cell line. Based on the GEO dataset, potential biomarker genes were proposed and the enriched biological processes as well as signaling pathways were further investigated. A protein‑protein interaction network of target genes was established. In the clinical specimens, the functions of the primary candidate, FBJ murine osteosarcoma viral oncogene homolog B (FOSB), were evaluated by reverse transcription‑quantitative (RT‑q)PCR and western blot analysis. A Cell Counting Kit‑8 (CCK‑8) assay was used for a functional study on FOSB. The results indicated that, compared with non‑tumor bile duct tissues, primary CCA samples had 676 differentially expressed genes, including 277 downregulated and 399 upregulated ones. Among these, HBD, FOSB, HBB, ITIH2, FCGBP, MT1JP, PIJR, SLC38A1, COL10A1 and MMP19 were determined to be the most significant DEGs. At the same time, upregulated genes were enriched in ‘vasculature development’ and ‘IL‑17 signaling pathways’. Downregulated genes were enriched in ‘extracellular matrix progress’ and ‘glucuronate signaling pathway’. The patients with CCA displayed decreased levels of hemoglobin. Compared with paracancerous tissues, CCA cancerous tissues exhibited increased RNA and protein expression levels of FOSB according to RT‑qPCR and western blot analysis, respectively. Furthermore, FOSB expression influenced the proliferation/viability of the CCA cell line HUCCT1. In conclusion, the present study suggested that the FOSB gene may serve as a primary biomarker candidate for CCA, providing a valuable reference for its clinical implementation.

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