AUTHOR=Kou Fushun , Cheng Yuan , Shi Lei , Liu Jiajing , Liu Yuyue , Shi Rui , Peng Guiying , Li Junxiang TITLE=LCN2 as a Potential Diagnostic Biomarker for Ulcerative Colitis-Associated Carcinogenesis Related to Disease Duration JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.793760 DOI=10.3389/fonc.2021.793760 ISSN=2234-943X ABSTRACT=Background

Patients with long-duration ulcerative colitis (UC) had a higher risk of developing ulcerative colitis-associated carcinogenesis (UCAC) when compared to those with short-duration UC. This study aimed to discover the biomarker for cancer surveillance related to disease duration.

Methods

The microarrays were divided into short-duration (<10 years) UC, long-duration (≥10 years) UC, UCAC, and normal groups in the Gene Expression Omnibus (GEO) datasets. Differentially expressed genes (DEGs) of GEO and the hub genes of the selected weighted gene co-expression network analysis (WGCNA) were intersected to obtain the overlapping genes. Among these genes, the key gene was identified by using the protein–protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the cytoHubba of Cytoscape, and the expression levels. Also, immunofluorescence of human colonic mucosa and animal experiment were used to validate the expression trend of the key gene in the progress of UC developing into UCAC.

Results

Lipocalin-2 (LCN2) was more relevant with disease duration of UC and significantly negatively correlated with the risk of UCAC. The expression level of LCN2 in short-duration UC was higher than that of long-duration UC (P < 0.01), long-duration UC was higher than that of UCAC (P = 0.001), and UC and UCAC were all higher than that of the normal (P < 0.001). We then discovered that the expression trend of LCN2 in blood and stool samples was consistent with that in colorectal mucosa.

Conclusion

The research indicates that LCN2 could be a novel biomarker to evaluate cancer surveillance related to disease duration of developing UC into UCAC. Compared with that of blood samples, stool detection of LCN2 may have more advantages for diagnosis value of early stage of UCAC as a complement to colonoscopy surveillance.