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Effect of CD274 (PD-L1) overexpression on survival outcomes in 10 specific cancers: a systematic review and meta-analysis
  1. Ji Hyun Park1,
  2. Claudio Luchini2,
  3. Alessia Nottegar2,
  4. Kalthoum Tizaoui3,
  5. Ai Koyanagi4,5,6,
  6. Shuji Ogino7,8,9,10,
  7. Jae Il Shin11,
  8. Beom Jin Lim12,
  9. Lee Smith13
  1. 1 Yonsei University College of Medicine, Seoul, South Korea
  2. 2 Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy
  3. 3 Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
  4. 4 Research and Development Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Spain
  5. 5 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain
  6. 6 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
  7. 7 Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  8. 8 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  9. 9 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  10. 10 Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts, USA
  11. 11 Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea
  12. 12 Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
  13. 13 Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK
  1. Correspondence to Dr Jae Il Shin, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea (the Republic of); shinji{at}yuhs.ac; Dr Beom Jin Lim, Department of Pathology, Yonsei University College of Medicine, Seoul, Korea (the Republic of); BJLIM{at}yuhs.ac

Abstract

Aim The prognostic role of CD274 (programmed cell death ligand 1 (PD-L1)) overexpression has been examined in many studies. However, the results are controversial and conflicting. The present study aims to investigate the potential role of CD274 (PD-L1) immunohistochemical overexpression as a prognostic marker in malignant tumours.

Methods We searched PubMed, Embase and Web of Science from inception to December 2021 to identify potentially eligible studies. The pooled HRs with 95% CIs were calculated to identify the association between CD274 (PD-L1) overexpression and overall survival (OS), cancer-specific survival, disease-free survival, recurrence-free survival and progression-free survival in 10 lethal malignant tumours. Heterogeneity and publication bias were also analysed.

Results The study included 57 322 patients from 250 eligible studies (241 articles). The meta-analysis by tumour type using multivariate HR revealed worse OS in non-small cell lung cancer (HR 1.41, 95% CI 1.19 to 1.68), hepatocellular carcinoma (HR 1.75, 95% CI 1.11 to 2.74), pancreatic cancer (HR 1.84, 95% CI 1.12 to 3.02), renal cell carcinoma (HR 1.55, 95% CI 1.12 to 2.14) and colorectal cancer (HR 1.46, 95% CI 1.14 to 1.88). Estimated HRs showed associations between CD274 (PD-L1) overexpression and worse prognosis across different types of tumours in various survival endpoints, but no inverse correlation was identified. The heterogeneity for most of the pooled results was high.

Conclusions This large meta-analysis suggests that CD274 (PD-L1) overexpression is a potential biomarker for multiple types of cancers. However, further studies are needed to reduce high heterogeneity.

PROSPERO registration number CRD42022296801.

  • NEOPLASMS
  • IMMUNOHISTOCHEMISTRY
  • Medical Oncology

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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Footnotes

  • Handling editor Yoh Zen.

  • Contributors Conceptualisation: JHP, JIS, BJL, LS and AK; methodology: JIS, BJL, CL and SO; literature review and data extraction: JHP, JIS, BJL and CL; original draft preparation, JHP, JIS and BJL; data interpretation and discussion, manuscript editing and approval of the final version of the manuscript: all authors, guarantor: JIS and BJL.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.