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

Yuanmin He; Hongliang Liu; Sheng Luo; Christopher I Amos; Jeffrey E Lee; Keming Yang; Abrar A Qureshi; Jiali Han; Qingyi Wei

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

Am J Cancer Res. 2021 Jun 15;11(6):3252-3262. eCollection 2021.

Authors

Yuanmin He^{1

2

3}, Hongliang Liu^{2

3}, Sheng Luo⁴, Christopher I Amos⁵, Jeffrey E Lee⁶, Keming Yang⁷, Abrar A Qureshi^{8

9}, Jiali Han^{7

10}, Qingyi Wei^{2

3

11}

Affiliations

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.

PMID: 34249459
PMCID: PMC8263692

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.

Keywords: Cutaneous melanoma; myeloid cell; prognostic factors; single-nucleotide polymorphism; survival.