Classification of node-positive melanomas into prognostic subgroups using keratin, immune, and melanogenesis expression patterns.
Carcinogenesis
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Immunity
/ genetics
Kallikreins
/ genetics
Male
Melanins
/ biosynthesis
Melanoma
/ classification
Melanosomes
/ genetics
Muscle Proteins
/ genetics
Neoplasm Metastasis
/ genetics
Neoplasm Proteins
/ genetics
RNA-Seq
Receptors, Immunologic
/ genetics
Survival Analysis
Transcriptome
/ genetics
Tripartite Motif Proteins
/ genetics
Ubiquitin-Protein Ligases
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
10
06
2020
accepted:
18
01
2021
revised:
08
11
2020
pubmed:
11
2
2021
medline:
16
10
2021
entrez:
10
2
2021
Statut:
ppublish
Résumé
Cutaneous melanoma tumors are heterogeneous and show diverse responses to treatment. Identification of robust molecular biomarkers for classifying melanoma tumors into clinically distinct and homogenous subtypes is crucial for improving the diagnosis and treatment of the disease. In this study, we present a classification of melanoma tumors into four subtypes with different survival profiles based on three distinct gene expression signatures: keratin, immune, and melanogenesis. The melanogenesis expression pattern includes several genes that are characteristic of the melanosome organelle and correlates with worse survival, suggesting the involvement of melanosomes in melanoma aggression. We experimentally validated the secretion of melanosomes into surrounding tissues by melanoma tumors, which potentially affects the lethality of metastasis. We propose a simple molecular decision tree classifier for predicting a tumor's subtype based on representative genes from the three identified signatures. Key predictor genes were experimentally validated on melanoma samples taken from patients with varying survival outcomes. Our three-pattern approach for classifying melanoma tumors can contribute to advancing the understanding of melanoma variability and promote accurate diagnosis, prognostication, and treatment.
Identifiants
pubmed: 33564068
doi: 10.1038/s41388-021-01665-0
pii: 10.1038/s41388-021-01665-0
pmc: PMC7946641
doi:
Substances chimiques
Melanins
0
Muscle Proteins
0
Neoplasm Proteins
0
Receptors, Immunologic
0
TIGIT protein, human
0
Tripartite Motif Proteins
0
TRIM63 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
KLK8 protein, human
EC 3.4.21.-
Kallikreins
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1792-1805Subventions
Organisme : European Research Council
ID : 726225
Pays : International
Références
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
BMC Bioinformatics. 2019 Dec 26;20(1):732
pubmed: 31878868
Oncotarget. 2015 May 20;6(14):12297-309
pubmed: 25909218
Nat Cell Biol. 2016 Sep;18(9):1006-17
pubmed: 27548915
Biochim Biophys Acta. 2013 Dec;1833(12):3471-3480
pubmed: 23792051
Breast Cancer Res. 2016 Jul 07;18(1):74
pubmed: 27386846
Exp Dermatol. 2009 Jul;18(7):586-95
pubmed: 19320736
Int J Mol Sci. 2016 Jul 15;17(7):
pubmed: 27428965
Biomed Pharmacother. 2017 Apr;88:595-602
pubmed: 28142115
Nat Rev Cancer. 2016 Jun;16(6):345-58
pubmed: 27125352
Cell Rep. 2015 Oct 27;13(4):840-853
pubmed: 26489459
Nat Rev Mol Cell Biol. 2007 Oct;8(10):786-97
pubmed: 17878918
J Natl Cancer Inst. 2009 Sep 16;101(18):1259-71
pubmed: 19704071
BMC Bioinformatics. 2009 Feb 03;10:48
pubmed: 19192299
Dermatol Pract Concept. 2017 Apr 30;7(2):1-6
pubmed: 28515985
BMC Bioinformatics. 2005 Sep 21;6:232
pubmed: 16176576
Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9903-7
pubmed: 16777967
Genome Res. 2016 May;26(5):601-11
pubmed: 26907635
Br J Cancer. 2016 Jul 12;115(2):145-55
pubmed: 27336610
Elife. 2014 Dec 16;3:e04543
pubmed: 25513726
Clin Cancer Res. 2010 Jul 1;16(13):3356-67
pubmed: 20460471
Mol Oncol. 2011 Apr;5(2):124-36
pubmed: 21482206
Pigment Cell Melanoma Res. 2009 Dec;22(6):740-9
pubmed: 19725928
Trends Mol Med. 2006 Sep;12(9):406-14
pubmed: 16899407
Nature. 2007 Feb 22;445(7130):843-50
pubmed: 17314970
J Clin Invest. 2015 May;125(5):2046-58
pubmed: 25866972
Trends Immunol. 2017 Jan;38(1):20-28
pubmed: 27793572
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Oncotarget. 2015 May 10;6(13):11683-93
pubmed: 25871393
J Med Syst. 2002 Oct;26(5):445-63
pubmed: 12182209
Nat Protoc. 2010 Feb;5(2):303-22
pubmed: 20134430
Int J Oncol. 2018 Apr;52(4):1071-1080
pubmed: 29532857
BMJ. 2004 May 1;328(7447):1073
pubmed: 15117797
Cell. 2015 Jun 18;161(7):1681-96
pubmed: 26091043
Cancer Cell. 2002 Oct;2(4):275-8
pubmed: 12398891
Cancer Res. 2006 Dec 15;66(24):11763-70
pubmed: 17178872
Nat Rev Cancer. 2017 Jul;17(7):393-394
pubmed: 28450704
J Am Acad Dermatol. 2019 Jan;80(1):208-250
pubmed: 30392755
Cancer Cell. 2005 Dec;8(6):439-41
pubmed: 16338657
Clin Cancer Res. 2006 Mar 1;12(5):1487-93
pubmed: 16533772
Mol Biol Cell. 2001 Nov;12(11):3451-64
pubmed: 11694580
Exp Dermatol. 2009 Nov;18(11):934-8
pubmed: 19645853
BMC Med Genomics. 2011 Oct 27;4:76
pubmed: 22032772
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
J Invest Dermatol. 2016 Dec;136(12):2502-2505
pubmed: 27345472