Cargando…
Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness
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. MET...
Autor principal: | |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Saudi Medical Journal
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506648/ https://www.ncbi.nlm.nih.gov/pubmed/30957125 http://dx.doi.org/10.15537/smj.2019.4.23380 |
_version_ | 1783416893767417856 |
---|---|
author | Alsagaby, Suliman A. |
author_facet | Alsagaby, Suliman A. |
author_sort | Alsagaby, Suliman A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6506648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Saudi Medical Journal |
record_format | MEDLINE/PubMed |
spelling | pubmed-65066482019-05-22 Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness Alsagaby, Suliman A. Saudi Med J Original Article 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. Saudi Medical Journal 2019 /pmc/articles/PMC6506648/ /pubmed/30957125 http://dx.doi.org/10.15537/smj.2019.4.23380 Text en Copyright: © Saudi Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Alsagaby, Suliman A. Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
title | Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
title_full | Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
title_fullStr | Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
title_full_unstemmed | Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
title_short | Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
title_sort | transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506648/ https://www.ncbi.nlm.nih.gov/pubmed/30957125 http://dx.doi.org/10.15537/smj.2019.4.23380 |
work_keys_str_mv | AT alsagabysulimana transcriptomicsbasedvalidationoftherelatednessofheterogeneousnuclearribonucleoproteinstochroniclymphocyticleukemiaaspotentialbiomarkersofthediseaseaggressiveness |