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Peer-reviewedCC BYPloS one

A public-data audit of transcriptomic prognostic transportability in R-CHOP-treated diffuse large B-cell lymphoma.

  • Yongqing Li1
  • Guowei Xiong2
  • Wenhao Feng3
  • Qi Chen4
  • Yingying Qin5,6
  • Haoyun Hong7
  • Lin Lin8
8 affiliations
  1. 1Department of Hematology, Jieyang People's Hospital, Jieyang, Guangdong, China.
  2. 2Department of Laboratory Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  3. 3Pathology and Laboratory Center, Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  4. 4Department of Laboratory Medicine, Jieyang People's Hospital, Jieyang, Guangdong, China.
  5. 5Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
  6. 6Jiexi County Second People's Hospital, Jieyang, Guangdong, China.
  7. 7Faculty of Medicine, School of Pharmacy, Medical Science Division, Macau University of Science and Technology, Macau SAR, China.
  8. 8Department of Laboratory Medicine, Rongcheng District Central Hospital, Jieyang, Guangdong, China.
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Abstract

Gene-expression biomarkers for diffuse large B-cell lymphoma (DLBCL) are often transported across retrospective cohorts that differ in treatment, assay platform, and clinical annotation. Using REMARK as the reporting framework, we audited prognostic associations with fixed scoring rules. Four Gene Expression Omnibus cohorts were harmonized for survival analysis. Treatment context was assessed after outcome-blind transcriptional state discovery. A directly mapped five-gene historical benchmark was evaluated with continuous Cox models in four R-CHOP cohorts. A 76-gene program selected in GSE31312 and GSE10846 served as a case study of two-cohort discovery, with GSE87371 as the only full-coverage independent evaluation and GSE32918 as a cross-platform sensitivity analysis. Coverage ablation, technical replicates, matched random programs, meta-analysis, and clinical-increment analyses assessed attenuation. The survival analyses included 470, 232, 87, and 140 patients. State composition was strongly associated with CHOP versus R-CHOP context in GSE10846 (Cramer's V = 0.986). The historical score's unadjusted random-effects hazard ratio (HR) was 1.35 (95% confidence interval 1.04-1.75); the prediction interval crossed the null (0.77-2.37). Common age/sex adjustment yielded HR 1.27 (1.05-1.54), with a prediction interval of 0.94-1.72. The 76-gene program was not independently validated in GSE87371 (unadjusted HR 1.23, 0.87-1.75; IPI/COO-adjusted HR 0.88, 0.56-1.40; age/sex-adjusted HR 1.09, 0.76-1.55). Its effect exceeded most matched random programs, but cross-cohort attenuation was pronounced and estimated clinical increment was negligible. With only 32 validation events, modest effects remain compatible with the data. Public DLBCL transcriptomic associations can be cohort-specific despite fixed scoring rules. Independent full-coverage evaluation and transparent treatment and platform audits should precede claims of general prognostic utility.

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Cite

BibTeXRIS
BibTeX
@article{li2026publicdata,
  title = {{A public-data audit of transcriptomic prognostic transportability in R-CHOP-treated diffuse large B-cell lymphoma.}},
  author = {Yongqing Li and Guowei Xiong and Wenhao Feng and Qi Chen and Yingying Qin and Haoyun Hong and Lin Lin},
  journal = {PloS one},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0360937},
  url = {https://europepmc.org/article/MED/42912792},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A public-data audit of transcriptomic prognostic transportability in R-CHOP-treated diffuse large B-cell lymphoma.
AU  - Yongqing Li
AU  - Guowei Xiong
AU  - Wenhao Feng
AU  - Qi Chen
AU  - Yingying Qin
AU  - Haoyun Hong
AU  - Lin Lin
PY  - 2026
DA  - 2026/10/23
JO  - PloS one
DO  - 10.1371/journal.pone.0360937
UR  - https://europepmc.org/article/MED/42912792
AB  - Gene-expression biomarkers for diffuse large B-cell lymphoma (DLBCL) are often transported across retrospective cohorts that differ in treatment, assay platform, and clinical annotation. Using REMARK as the reporting framework, we audited prognostic associations with fixed scoring rules. Four Gene Expression Omnibus cohorts were harmonized for survival analysis. Treatment context was assessed after outcome-blind transcriptional state discovery. A directly mapped five-gene historical benchmark was evaluated with continuous Cox models in four R-CHOP cohorts. A 76-gene program selected in GSE31312 and GSE10846 served as a case study of two-cohort discovery, with GSE87371 as the only full-coverage independent evaluation and GSE32918 as a cross-platform sensitivity analysis. Coverage ablation, technical replicates, matched random programs, meta-analysis, and clinical-increment analyses assessed attenuation. The survival analyses included 470, 232, 87, and 140 patients. State composition was strongly associated with CHOP versus R-CHOP context in GSE10846 (Cramer's V = 0.986). The historical score's unadjusted random-effects hazard ratio (HR) was 1.35 (95% confidence interval 1.04-1.75); the prediction interval crossed the null (0.77-2.37). Common age/sex adjustment yielded HR 1.27 (1.05-1.54), with a prediction interval of 0.94-1.72. The 76-gene program was not independently validated in GSE87371 (unadjusted HR 1.23, 0.87-1.75; IPI/COO-adjusted HR 0.88, 0.56-1.40; age/sex-adjusted HR 1.09, 0.76-1.55). Its effect exceeded most matched random programs, but cross-cohort attenuation was pronounced and estimated clinical increment was negligible. With only 32 validation events, modest effects remain compatible with the data. Public DLBCL transcriptomic associations can be cohort-specific despite fixed scoring rules. Independent full-coverage evaluation and transparent treatment and platform audits should precede claims of general prognostic utility.
SN  - 1932-6203
ER  -