Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness

Abstract

Objectives:

To use independent transcriptomics data sets of cancer patients with prognostic information from public repositories to validate the relevance of our previously described chronic lymphocytic leukemia (CLL)-related proteins at the level of transcription (mRNA) to the prognosis of CLL.

Methods:

This is a validation study that was conducted at Majmaah University, Kingdom of Saudi Arabia between January-2017 and July-2018. Two independent data sets of CLL transcriptomics from Gene Expression Omnibus (GEO) with time-to-first treatment (TTFT) data (GSE39671; 130 patients) and information about overall survival (OS) (GSE22762; 107 patients) were used for the validation analyses. To further investigate the relatedness of a transcript of interest to other neoplasms, 6 independent data sets of cancer transcriptomics with prognostic information (1865 patients) from the cancer genomics atlas (TCGA) were used. Pathway-enrichment analyses were conducted using Reactome; and correlation analyses of gene expression were performed using Pearson score.

Results:

Nine of the CLL-related proteins exhibited transcript expression that predicted TTFT and 7 of the CLL-related proteins showed mRNA levels that predicted OS in CLL patients ( p≤0.05). Of these transcripts, 8 were different types of heterogeneous nuclear ribonucleoproteins ( HNRNPs); and 2 ( HNRNPUL2 and HIST1C1H) retained prognostic significance in the 2 independent data sets. Furthermore, genes that enriched CLL-related pathways ( p≤0.05; false discovery rate [FDR] ≤0.05) were found to correlate with the expression of HNRNPUL2 (Pearson score: ≥0.50; p<0.00001). Finally, increased expression of HNRNPUL2 was indicative of poor prognosis of various types of cancer other than CLL ( p<0.05).

Conclusion:

The cognate transcripts of 14 of our CLL-related proteins significantly predicted CLL prognosis.