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Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia

Overview of attention for article published in Clinical Epigenetics, May 2017
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Title
Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia
Published in
Clinical Epigenetics, May 2017
DOI 10.1186/s13148-017-0356-0
Pubmed ID
Authors

Lata Rani, Nitin Mathur, Ritu Gupta, Ajay Gogia, Gurvinder Kaur, Jaspreet Kaur Dhanjal, Durai Sundar, Lalit Kumar, Atul Sharma

Abstract

In chronic lymphocytic leukemia (CLL), epigenomic and genomic studies have expanded the existing knowledge about the disease biology and led to the identification of potential biomarkers relevant for implementation of personalized medicine. In this study, an attempt has been made to examine and integrate the global DNA methylation changes with gene expression profile and their impact on clinical outcome in early stage CLL patients. The integration of DNA methylation profile (n = 14) with the gene expression profile (n = 21) revealed 142 genes as hypermethylated-downregulated and; 62 genes as hypomethylated-upregulated in early stage CLL patients compared to CD19+ B-cells from healthy individuals. The mRNA expression levels of 17 genes identified to be differentially methylated and/or differentially expressed was further examined in early stage CLL patients (n = 93) by quantitative real time PCR (RQ-PCR). Significant differences were observed in the mRNA expression of MEIS1, PMEPA1, SOX7, SPRY1, CDK6, TBX2, and SPRY2 genes in CLL cells as compared to B-cells from healthy individuals. The analysis in the IGHV mutation based categories (Unmutated = 39, Mutated = 54) revealed significantly higher mRNA expression of CRY1 and PAX9 genes in the IGHV unmutated subgroup (p < 0.001). The relative risk of treatment initiation was significantly higher among patients with high expression of CRY1 (RR = 1.91, p = 0.005) or PAX9 (RR = 1.87, p = 0.001). High expression of CRY1 (HR: 3.53, p < 0.001) or PAX9 (HR: 3.14, p < 0.001) gene was significantly associated with shorter time to first treatment. The high expression of PAX9 gene (HR: 3.29, 95% CI 1.172-9.272, p = 0.016) was also predictive of shorter overall survival in CLL. The DNA methylation changes associated with mRNA expression of CRY1 and PAX9 genes allow risk stratification of early stage CLL patients. This comprehensive analysis supports the concept that the epigenetic changes along with the altered expression of genes have the potential to predict clinical outcome in early stage CLL patients.

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Mendeley readers

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The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 24%
Researcher 8 20%
Student > Bachelor 3 7%
Librarian 2 5%
Professor > Associate Professor 2 5%
Other 6 15%
Unknown 10 24%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 22%
Biochemistry, Genetics and Molecular Biology 6 15%
Medicine and Dentistry 4 10%
Engineering 3 7%
Immunology and Microbiology 2 5%
Other 4 10%
Unknown 13 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 May 2019.
All research outputs
#20,428,633
of 22,981,247 outputs
Outputs from Clinical Epigenetics
#1,119
of 1,262 outputs
Outputs of similar age
#275,204
of 316,101 outputs
Outputs of similar age from Clinical Epigenetics
#26
of 30 outputs
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