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Genetic variants of EML1 and HIST1H4E in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival.

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机构: [1]Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China [2]Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA [3]Department of Population Health Sciences, Duke University School of Medicine, Durham, NC 27710, USA [4]Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA [5]Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, USA [6]Department of Surgical Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA [7]Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN 46202, USA [8]Department of Dermatology, Rhode Island Hospital, Providence, RI 02901, USA [9]Warren Alpert Medical School at Brown University, Providence, RI 02901, USA [10]The Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [11]Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
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关键词: Cutaneous melanoma myeloid cell single-nucleotide polymorphism survival prognostic factors

摘要:
Both in vivo and in vitro evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown.we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients.we identified two SNPs (EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, P=0.001) and 1.66 (1.22-2.26, P=0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets (P trend<0.001 and 0.002, respectively). Additional functional analysis revealed that both EML1 rs10151787 G and HIST1H4E rs2069018 C alleles were associated with elevated mRNA expression levels in normal tissues.Our findings suggest that EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS.AJCR Copyright © 2021.

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
第一作者:
第一作者机构: [1]Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China [2]Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA [3]Department of Population Health Sciences, Duke University School of Medicine, Durham, NC 27710, USA
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通讯机构: [2]Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA [3]Department of Population Health Sciences, Duke University School of Medicine, Durham, NC 27710, USA [11]Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA [*1]Duke Cancer Institute, Duke University Medical Center, 905 South LaSalle Street, Durham 27710, North Carolina, USA.
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