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Tytuł pozycji:

Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study.

Tytuł :
Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study.
Autorzy :
Wang Q; Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital and Department of Epidemiology and Health Statistics School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Ye Y; Center for Clinical Big Data and Analytics, Bioinformatics and Big Data, The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou, 310058, PR China.
Yu H; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lin SH; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Tu H; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Liang D; Department of Pharmaceutical Sciences, Texas Southern University, Houston, TX, USA.
Chang DW; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Huang M; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wu X; Center for Clinical Big Data and Analytics, Bioinformatics and Big Data, The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou, 310058, PR China. .
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Źródło :
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 Mar; Vol. 70 (3), pp. 701-712. Date of Electronic Publication: 2020 Sep 09.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York, NY : Springer International, c1982-
MeSH Terms :
Genetic Variation*
Immune Checkpoint Proteins/*metabolism
Prostatic Neoplasms/*etiology
Prostatic Neoplasms/*metabolism
Aged ; Biomarkers ; Cohort Studies ; Disease Progression ; Disease Susceptibility ; Genotype ; Humans ; Immune Checkpoint Proteins/blood ; Immune Checkpoint Proteins/genetics ; Immunophenotyping ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prostatic Neoplasms/mortality ; Prostatic Neoplasms/pathology ; Receptors, Antigen, B-Cell/metabolism
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Grant Information :
P50 CA140388 United States CA NCI NIH HHS; Duncan Family Institute MD Anderson Cancer Center Prostate Cancer SPORE and Center for Translational and Public Health Genomics (CTPHG); P50 CA140388 United States CA NCI NIH HHS
Contributed Indexing :
Keywords: Aggressiveness; Biochemical recurrence; Genetic variations; Localized prostate cancer; Progression free survival; Serum immune checkpoint
Substance Nomenclature :
0 (Biomarkers)
0 (Immune Checkpoint Proteins)
0 (Receptors, Antigen, B-Cell)
Entry Date(s) :
Date Created: 20200910 Date Completed: 20210308 Latest Revision: 20210310
Update Code :
20210310
PubMed Central ID :
PMC7907032
DOI :
10.1007/s00262-020-02718-1
PMID :
32909077
Czasopismo naukowe
Background: The clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa.
Methods: We profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-data from ArrayExpress and TCGA was employed to validate and to probe functional data. Patients were enrolled and tumor aggressiveness, biochemical recurrence (BCR), and progression information were obtained. Statistical analyses were performed analyzing associations between serum biomarkers, genotypes, mRNA and outcomes.
Results: We showed that serum (s)BTLA and sTIM3 levels were associated with PCa aggressiveness (P < 0.05). sCD28, sCD80, sCTLA4, sGITR, sHVEM and sIDO correlated with both BCR and progression risks (all P < 0.05). We further identified ICK variants were significantly associated with aggressiveness, BCR and progression. Among them, 4 SNPs located in CD80 (rs7628626, rs12695388, rs491407, rs6804441) were not only associated with BCR and progression risk, but also correlated with sCD80 level (P < 0.01). rs491407 was further validated in an independent cohort. The CD80 mRNA expression was associated with BCR (HR, 1.85, 95% CI 1.06-3.22, P = 0.03) in meta-analysis of validation cohorts.
Conclusion: We highlight the prognostic value of serum ICK-related proteins for predicting aggressiveness, BCR and progression of PCa. The genetic variations and mRNA expression in CD80 could be predictors and potential targets of localized PCa.

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