Yuanmin He1,2,3, Hongliang Liu2,3, Sheng Luo4, Christopher I Amos5, Jeffrey E Lee6, Keming Yang7, Abrar A Qureshi8,9, Jiali Han7,10, Qingyi Wei2,3,11. 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.
Abstract
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest that EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS. AJCR
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. METHODS: we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CMpatients and replicated the findings in another dataset of 409 CMpatients. RESULTS: 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. CONCLUSIONS: Our findings suggest that EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS. AJCR
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