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pmid:30957125

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

Suliman A Alsagaby

Saudi medical journal · 2019 doi:10.15537/smj.2019.4.23380

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title
Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness.
doi
10.15537/smj.2019.4.23380
pmid
30957125
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Suliman A Alsagaby
journal
Saudi medical journal
year
2019
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 lessthan 0.00001). Finally, increased expression of HNRNPUL2 was indicative of poor prognosis of various types of cancer other than CLL (p less than 0.05). Conclusion: The cognate transcripts of 14 of our CLL-related proteins significantly predicted CLL prognosis.
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Prism Graphpad software was used to create Kaplan-Meier curves of TTFT, RFS, and OS; the Log-rank test was used to calculate p-values and hazard ratios (HRs).
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Prism Graphpad software was used to create Kaplan-Meier curves of TTFT, RFS, and OS; the Log-rank test was used to calculate p-values and hazard ratios (HRs).
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The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). The data set GSE39671 was generated from 130 CLL patients and the data set GSE22762 was reported from 107 CLL patients.
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The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). The data set GSE39671 was generated from 130 CLL patients and the data set GSE22762 was reported from 107 CLL patients.
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Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 2 items
[0]
GSE39671
[1]
GSE22762
resolved_accessions array · 2 items
[0]
GSE39671
[1]
GSE22762
statements array · 1 item
[0]
The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). The data set GSE39671 was generated from 130 CLL patients and the data set GSE22762 was reported from 107 CLL patients.
basis
The paper names GSE39671, GSE22762 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
logrank_test
assets array · 4 items
[0]
source:pmid:30957125
[1]
data:geo:GSE22762
[2]
asset:table:pmid:30957125:1
[3]
asset:table:pmid:30957125:2
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE22762
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:14:30Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
3
usage object · 3 fields
prompt_tokens
19447
completion_tokens
1480
cached_tokens
6664
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:30957125
type
paper
label
pmid:30957125
[1] object · 3 fields
id
source:pmid:30957125
type
manuscript
label
PMID 30957125 full text
[2] object · 3 fields
id
data:geo:GSE22762
type
dataset
label
GEO GSE22762
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:30957125
type
paper
label
pmid:30957125
[1] object · 3 fields
id
source:pmid:30957125
type
manuscript
label
PMID 30957125 full text
[2] object · 3 fields
id
data:geo:GSE22762
type
dataset
label
GEO GSE22762
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-30957125
type
extraction
used array · 1 item
[0]
source:pmid:30957125
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE22762
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE22762
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:30957125
parent_hash
sha256:e38ea27b493e562a35cfcfe357fbc5895b52fa23f4d2d4b973e54334a213c676
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE22762 licence not read
[1]
asset:data:geo:GSE22762 not downloaded
[2]
asset:data:geo:GSE39671 licence not read
[3]
asset:data:geo:GSE39671 not downloaded
[4]
execution.not_run
[5]
review.human_critique
[6]
review.independent_reader
[7]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
logrank_test
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Prism Graphpad software was used to create Kaplan-Meier curves of TTFT, RFS, and OS; the Log-rank test was used to calculate p-values and hazard ratios (HRs).
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30957125", "kind": "science-record", "revision": 7, "content_hash": "sha256:6bd6224a539e96d343ab6f9d29b97d26106efe1ac100f30760f258119a532dbf", "created_at": "2026-11-01T15:40:44Z", "updated_at": "2026-11-01T21:22:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness.", "doi": "10.15537/smj.2019.4.23380", "pmid": "30957125", "authors": ["Suliman A Alsagaby"], "journal": "Saudi medical journal", "year": 2019, "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 lessthan 0.00001). Finally, increased expression of HNRNPUL2 was indicative of poor prognosis of various types of cancer other than CLL (p less than 0.05). Conclusion: The cognate transcripts of 14 of our CLL-related proteins significantly predicted CLL prognosis.", "claims": [{"id": "claim-method", "statement": "Prism Graphpad software was used to create Kaplan-Meier curves of TTFT, RFS, and OS; the Log-rank test was used to calculate p-values and hazard ratios (HRs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30957125", "locator": "sections[9] \"Statistical analyses\" paragraph 2", "quote": "Prism Graphpad software was used to create Kaplan-Meier curves of TTFT, RFS, and OS; the Log-rank test was used to calculate p-values and hazard ratios (HRs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). The data set GSE39671 was generated from 130 CLL patients and the data set GSE22762 was reported from 107 CLL patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30957125", "locator": "sections[6] \"Transcriptomics data sets from GEO\" paragraph 2", "quote": "The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). The data set GSE39671 was generated from 130 CLL patients and the data set GSE22762 was reported from 107 CLL patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30957125"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE22762"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE22762"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30957125", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.15537/smj.2019.4.23380", "sha256": "sha256:874965cc99d7518006f1a0c96210f5049a9a1633de220a7720cb1938296ea678", "bytes": 26870, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.15537/smj.2019.4.23380", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6506648", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE22762", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22762", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22762", "version": null, "note": "The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). The data set GSE39671 was generated from 130 CLL patients and the data set GSE22762 was reported from 107 CLL patients.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data set GSE39671 contained information of TTFT and the data set GSE22762 included details of OS for the individual patients. Both data sets were reported by independent authors and were based on Affymetrix Human Genome U133 Plus 2.0 Array (USA). 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