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PD-1 protein and ge...
PD-1 protein and gene expression in early breast cancer : Prognostic implications
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Zerdes, Ioannis (author)
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Matikas, Alexios (author)
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Lövrot, John (author)
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Sifakis, Emmanouil G. (author)
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Richard, Francois (author)
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Sotiriou, Christos (author)
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Rassidakis, George Z. (author)
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Bergh, Jonas C. S. (author)
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- Valachis, Antonis, 1984- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län
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Foukakis, Theodoros (author)
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(creator_code:org_t)
- American Society of Clinical Oncology, 2020
- 2020
- English.
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:15 Suppl.
- Related links:
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https://urn.kb.se/re...
Abstract
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- Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear.Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistochemistry in tissue microarrays) and mRNA levels in a retrospective patient cohort of 586 patients treated for early BC in Stockholm, Sweden between 1997-2005, ii) systematic review and trial-level meta-analysis of studies published in Medline, Embase, Cochrane Library and Web of Science Core Collection libraries on the prognostic value of PD-1 IHC expression, and iii) pooled analysis of transcriptomic data from 39 publicly available datasets for the prognostic capacity of PD-1 gene expression. Univariate and multivariable Cox regression models were used.Results: In the retrospective study cohort, PD-1 protein was significantly associated with biologically high-risk characteristics. PD-1 protein, but not gene expression, was correlated with improved overall survival (OS) (adjusted HR = 0.73, 95% CI 0.55 – 0.96, p = 0.023 and adjusted HR = 0.88, 95% CI 0.68 – 1.13, p = 0.307, respectively). In the trial-level meta-analysis, 4736 entries were initially identified and 15 studies, including our original cohort, fulfilled the predefined eligibility criteria. PD-1 IHC expression was not prognostic in unselected patients. However, a significant correlation to improved disease-free survival was seen within the triple-negative subtype (pooled multivariate HR = 0.57, 95% CI 0.29 – 0.90, p = 0.02). In the pooled gene expression analysis, PD-1 gene expression was associated with improved OS in the entire population (adjusted HR = 0.89, 95% CI 0.80 – 0.99, p = 0.025) and in basal-like (adjusted HR = 0.77, 95% CI 0.63 – 0.95, p = 0.014) tumors.Conclusions: PD-1 expression at the RNA and protein levels represent promising prognostic factors, especially in the triple-negative and basal-like subtypes. Standardization and further validation are needed prior to clinical implementation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Zerdes, Ioannis
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Matikas, Alexios
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Lövrot, John
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Sifakis, Emmanou ...
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Richard, Francoi ...
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Sotiriou, Christ ...
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show more...
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Rassidakis, Geor ...
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Bergh, Jonas C. ...
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Valachis, Antoni ...
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Foukakis, Theodo ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Journal of Clini ...
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Örebro University