Association of HOXA9 Promoter Hypomethylation With Colorectal Cancer

22 Pages Posted: 1 Apr 2019

See all articles by Jie Dai

Jie Dai

Ningbo University - Medical School

Ranran Pan

Ningbo University - Medical School

Cong Zhou

Ningbo University - Medical School

Xiuru Ying

Ningbo University - Medical School

Shiwei Duan

Ningbo University - Medical School

Date Written: December 28, 2018

Abstract

Background: The HOXA9 gene encodes a DNA-binding transcription factor that is closely related to cancer, including colorectal cancer (CRC). In this study, we first explored whether HOXA9 promoter methylation was associated with CRC.

Materials and Methods: Quantitative methylation-specific PCR (qMSP) was used to detect HOXA9 methylation levels in 76 patients with tumor tissues and paired adjacent non-tumor tissues. The percentage of methylation reference (PMR) was used to indicate the level of gene methylation.

Results: Our results showed that the methylation level of HOXA9 in tumor tissues was significantly lower than that of matched adjacent non-tumor tissues (median PMR, 4.61% vs 10.04%, P = 0.003). The similar significant difference was also found in 45 pairs of CRC samples from the Cancer Genome Atlas (TCGA) database (cg21942490, P = 0.039; cg22055728, P = 0.001). In addition, TCGA data analysis also showed a significant inverse correlation between HOXA9 methylation level and its gene expression (r = -0.438, P = 3.71E-59). Data analysis from Gene Expression Omnibus (GEO) showed that cells treated with demethylating reagent significantly up-regulated HOXA9 expression (fold change > 1.76, P = 0.009).

Conclusion: Our results showed that HOXA9 hypomethylation is significantly associated with the risk of CRC, and the molecular mechanism of HOXA9 hypomethylation-related carcinogenesis needs further study.

Keywords: HOXA9, Colorectal Cancer, DNA Methylation, Biomarker

Suggested Citation

Dai, Jie and Pan, Ranran and Zhou, Cong and Ying, Xiuru and Duan, Shiwei, Association of HOXA9 Promoter Hypomethylation With Colorectal Cancer (December 28, 2018). Available at SSRN: https://ssrn.com/abstract=3349506 or http://dx.doi.org/10.2139/ssrn.3349506

Jie Dai

Ningbo University - Medical School

818 Fenghua Road
Ningbo
China

Ranran Pan

Ningbo University - Medical School

818 Fenghua Road
Ningbo
China

Cong Zhou

Ningbo University - Medical School

818 Fenghua Road
Ningbo
China

Xiuru Ying

Ningbo University - Medical School

818 Fenghua Road
Ningbo
China

Shiwei Duan (Contact Author)

Ningbo University - Medical School ( email )

818 Fenghua Road
Ningbo
China

HOME PAGE: http://https://www.researchgate.net/profile/Shiwei_Duan

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