Oncogenic Wnt3a is a promising sensitive biomarker for monitoring hepatocarcinogenesis

Min Yao; Jian-Jun Wang; Xi-Yu Chen; Wen-Li Sai; Jie Yang; De-Feng Wang; Li Wang; Deng-Fu Yao

doi:10.1016/j.hbpd.2022.11.004

Oncogenic Wnt3a is a promising sensitive biomarker for monitoring hepatocarcinogenesis

Hepatobiliary Pancreat Dis Int. 2023 Jun;22(3):263-269. doi: 10.1016/j.hbpd.2022.11.004. Epub 2022 Nov 11.

Authors

Min Yao¹, Jian-Jun Wang², Xi-Yu Chen³, Wen-Li Sai⁴, Jie Yang⁵, De-Feng Wang⁴, Li Wang⁶, Deng-Fu Yao⁷

Affiliations

¹ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China; Department of Immunology, Medical School of Nantong University, Nantong 226001, China.
² Nantong Health College of Jiangsu Province, Nantong 226016, China.
³ Department of Immunology, Medical School of Nantong University, Nantong 226001, China.
⁴ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
⁵ Department of Molecular Biology, Life Science School of Nantong University, Nantong 226019, China.
⁶ Research Center for Intelligence Information Technology of Nantong University, Nantong 226019, China.
⁷ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: yaodf@ahnmc.com.

PMID: 36435702
DOI: 10.1016/j.hbpd.2022.11.004

Abstract

Background: The effective treatment for hepatocellular carcinoma (HCC) depends on early diagnosis. Previously, the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC cells and could be released into the circulation. In this study, we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC.

Methods: Sprague-Dawley rats (SD) were fed with diet 2-fluorenylacetamide (2-FAA, 0.05%) for inducing hepatocarcinogenesis, and grouped based on liver morphological alteration by Hematoxylin & Eosin (H&E) staining; rats fed with normal chow were used as normal control (NC). Total RNA and protein were purified from rat livers. Differently expressed genes (DEGs) or Wnt3a mRNA, cellular distribution, and Wnt3a protein levels were analyzed by whole genome microarray with signal logarithm ratio (SLR log₂^cy5/cy3), immunohistochemistry, and enzyme-linked immunosorbent assay, respectively.

Results: Models of rat hepatocarcinogenesis were successfully established based on liver histopathological H&E staining. Rats were divided into the cell degeneration (rDeg), precancerosis (rPre-C) and HCC (rHCC) groups. Total numbers of the up- and down-regulated DEGs with SLR ≥ 8 were 55 and 48 in the rDeg group, 268 and 57 in the rPre-C group, and 312 and 201 in the rHCC group, respectively. Significantly altered genes were involved in cell proliferation, signal transduction, tumor metastasis, and apoptosis. Compared with the NC group, Wnt3a mRNA was increased by 4.6 folds (P < 0.001) in the rDeg group, 7.4 folds (P < 0.001) in the rPre-C group, and 10.4 folds (P < 0.001) in the rHCC group; the positive rates of liver Wnt3a were 66.7% (P = 0.001) in the rDeg group, 100% (P < 0.001) in the rPre-C group, and 100% (P < 0.001) in the rHCC group, respectively. Also, there were significant differences of liver Wnt3a (P < 0.001) or serum Wnt3a (P < 0.001) among different groups.

Conclusions: Overexpression of Wnt3a was associated with rat hepatocarcinogenesis and it should be expected to be a promising monitoring biomarker for HCC occurrence at early stage.

Keywords: Dynamic expression; Hepatocarcinogenesis; Model; Monitoring; Wnt3a.

MeSH terms

Animals
Biomarkers, Tumor / metabolism
Carcinogenesis* / genetics
Carcinoma, Hepatocellular* / pathology
Liver Neoplasms* / pathology
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Wnt Signaling Pathway
Wnt3A Protein* / analysis

Substances

Biomarkers, Tumor
RNA, Messenger
Wnt3A Protein