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Published on: March 10, 2015
Elucidating biomarkers of carcinogenesis in ulcerative colitis: insight from Mendelian randomization and
Xiang Xiao1, Xuanyu Wu1, Tian Liu2
1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, No. 39, 12 Qiao Road, Jinniu District, Chengdu, 610072, Sichuan, China.
Background And Objective:
Ulcerative colitis (UC) is a recognised precursor to colorectal cancer (CRC), yet the underlying relationship to genetic predisposition remains unclear. This study aimed to assess the genetic susceptibility of UC in relation to CRC risk and to identify potential UC carcinogenesis biomarkers.
Methods:
We performed a MR study using summary statistics from genome-wide association studies of UC and CRC. Subsequently, we analysed transcriptome data of UC and CRC and conducted a bioinformatics analysis to identify biomarkers of the canceration of UC.
Results:
MR analysis revealed a significant increase in CRC risk associated with genetic susceptibility to UC (OR = 5.276, 95% CI = 1.778-15.652, P = 0.003). Subsequent bioinformatics analyses identified BATF and JDP2 as biomarkers of the carcinogenesis of UC. Upregulation of BATF (HR = 1.493, 95% CI = 1.048-2.126, P = 0.027) and JDP2 (HR = 1.443, 95% CI = 1.016-2.051, P = 0.041) correlated with poorer overall survival in CRC. Single-cell RNA-seq analysis revealed that Treg cell in the CRC microenvironment exhibited abnormal levels of BATF expression. Compared with the UC microenvironment, more Treg cells were distributed in the CRC microenvironment. In addition, significant Treg-T cell communication was observed in the CRC microenvironment.
Conclusion:
Genetic susceptibility to UC significantly correlated with an increased risk of CRC. BATF and JDP2 emerged as key biomarkers in the carcinogenesis of UC. Based on abnormal BATF expression at the single-cell level, Treg cell was identified as important cell involved in UC carcinogenesis.
