Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 9/2018

01-09-2018 | Original Article – Cancer Research

Molecular classification and subtype-specific characterization of skin cutaneous melanoma by aggregating multiple genomic platform data

Authors: Xiaofan Lu, Qianyuan Zhang, Yue Wang, Liya Zhang, Huiling Zhao, Chen Chen, Yaoyan Wang, Shengjie Liu, Tao Lu, Fei Wang, Fangrong Yan

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2018

Login to get access

Abstract

Purpose

Traditional classification of melanoma is widely utilized with little apparent results making the development of robust classifiers that can guide therapies an urgency. Successful seminal research on classification has provided a wider understanding of cancer from multiple molecular profiles, respectively. However, it may ignore the complementary nature of the information provided by different types of data, which motivated us to subtype melanoma by aggregating multiple genomic platform data.

Methods

Aggregating three omics data of 328 melanoma samples, melanoma subtyping was performed by three clustering methods. Differences across subtypes were extracted by functional enrichment, epigenetically silencing, gene mutations and clinical features. Subtypes were further distinguished by putative biomarkers.

Results

Functional enrichment of the subtype-specific differential expression genes endowed subtypes new designation: immune, melanin and ion, in which the first subtype was enriched for immune system, the second was characterized by melanin and pigmentation, and the third was enriched for ion-involved transmission process. Subtypes also differed in age, Breslow thickness, tumor site, mutation frequency of BRAF, PTGS2, CDKN2A, CDKN2B and incidence of epigenetically silencing for IL15RA, EPSTI1, LXN, CDKN1B genes.

Conclusions

Skin cutaneous melanoma can be robustly divided into three subtypes by SNFCC+. Compared with the TCGA classification derived from gene expression, the subtypes we presented share concordance, but new traits are excavated. Such a genomic classification offers insights to further personalize therapeutic decision-making and melanoma management.
Appendix
Available only for authorised users
Literature
go back to reference Allen D, Lepple-Wienhues A, Cahalan M (1997) Ion channel phenotype of melanoma cell lines. J Membr Biol 155:27–34CrossRefPubMed Allen D, Lepple-Wienhues A, Cahalan M (1997) Ion channel phenotype of melanoma cell lines. J Membr Biol 155:27–34CrossRefPubMed
go back to reference Austin PF, Cruse CW, Lyman G, Schroer K, Glass F, Reintgen DS (1994) Age as a prognostic factor in the malignant melanoma population. Ann Surg Oncol 1:487–494 Austin PF, Cruse CW, Lyman G, Schroer K, Glass F, Reintgen DS (1994) Age as a prognostic factor in the malignant melanoma population. Ann Surg Oncol 1:487–494
go back to reference Azimi F et al (2012) Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol 30:2678–2683CrossRefPubMed Azimi F et al (2012) Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol 30:2678–2683CrossRefPubMed
go back to reference Balch CM (1992) Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 8:400–414 Balch CM (1992) Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 8:400–414
go back to reference Balch CM et al (2001) Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634CrossRefPubMed Balch CM et al (2001) Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634CrossRefPubMed
go back to reference Bhatia P, Friedlander P, Zakaria EA, Kandil E (2015) Impact of BRAF mutation status in the prognosis of cutaneous melanoma: an area of ongoing research. Ann Transl Med 3:24PubMedPubMedCentral Bhatia P, Friedlander P, Zakaria EA, Kandil E (2015) Impact of BRAF mutation status in the prognosis of cutaneous melanoma: an area of ongoing research. Ann Transl Med 3:24PubMedPubMedCentral
go back to reference Bonafede E (2015) Differential expression analysis for sequence count data via mixtures of negative binomials. Alma Bonafede E (2015) Differential expression analysis for sequence count data via mixtures of negative binomials. Alma
go back to reference Brunet J-P, Tamayo P, Golub TR, Mesirov JP (2004) Metagenes and molecular pattern discovery using matrix factorization. Proc Natl Acad Sci 101:4164–4169 Brunet J-P, Tamayo P, Golub TR, Mesirov JP (2004) Metagenes and molecular pattern discovery using matrix factorization. Proc Natl Acad Sci 101:4164–4169
go back to reference ChantoôMe AL, Potier-Cartereau M, Roger SB, Vandier C, Soriani O, Joulin V (2013) Ion channels as promising therapeutic targets for melanoma. InTech 20:429–460 ChantoôMe AL, Potier-Cartereau M, Roger SB, Vandier C, Soriani O, Joulin V (2013) Ion channels as promising therapeutic targets for melanoma. InTech 20:429–460
go back to reference Cin H et al (2011) Oncogenic FAM131B–BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol 121:763–774CrossRefPubMed Cin H et al (2011) Oncogenic FAM131B–BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol 121:763–774CrossRefPubMed
go back to reference Clark WH, From L, Bernardino EA, Mihm MC (1969) The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–727PubMed Clark WH, From L, Bernardino EA, Mihm MC (1969) The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–727PubMed
go back to reference Fecher LA, Cummings SD, Keefe MJ, Alani RM (2007) Toward a molecular classification of melanoma. J Clin Oncol 25:1606–1620CrossRefPubMed Fecher LA, Cummings SD, Keefe MJ, Alani RM (2007) Toward a molecular classification of melanoma. J Clin Oncol 25:1606–1620CrossRefPubMed
go back to reference Fisher NM, Schaffer JV, Berwick M, Bolognia JL (2005) Breslow depth of cutaneous melanoma: impact of factors related to surveillance of the skin, including prior skin biopsies and family history of melanoma. J Am Acad Dermatol 53:393–406CrossRefPubMed Fisher NM, Schaffer JV, Berwick M, Bolognia JL (2005) Breslow depth of cutaneous melanoma: impact of factors related to surveillance of the skin, including prior skin biopsies and family history of melanoma. J Am Acad Dermatol 53:393–406CrossRefPubMed
go back to reference Garg K et al (2016) Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome. Human Pathol 54:157–164CrossRef Garg K et al (2016) Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome. Human Pathol 54:157–164CrossRef
go back to reference Gomez-Lira M et al (2014) Association of promoter polymorphism – 765G> C in the PTGS2 gene with malignant melanoma in Italian patients and its correlation to gene expression in dermal fibroblasts. Exp Dermatol 23:766–768CrossRefPubMed Gomez-Lira M et al (2014) Association of promoter polymorphism – 765G> C in the PTGS2 gene with malignant melanoma in Italian patients and its correlation to gene expression in dermal fibroblasts. Exp Dermatol 23:766–768CrossRefPubMed
go back to reference Haluska F, Pemberton T, Ibrahim N, Kalinsky K (2007) The RTK/RAS/BRAF/PI3K pathways in melanoma: biology, small molecule inhibitors, and potential applications. Semin Oncol 34:546–554CrossRefPubMed Haluska F, Pemberton T, Ibrahim N, Kalinsky K (2007) The RTK/RAS/BRAF/PI3K pathways in melanoma: biology, small molecule inhibitors, and potential applications. Semin Oncol 34:546–554CrossRefPubMed
go back to reference Hawkes JE et al (2013) Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree. J Dermatol Sci 69:30–37CrossRefPubMed Hawkes JE et al (2013) Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree. J Dermatol Sci 69:30–37CrossRefPubMed
go back to reference Inamdar GS, Madhunapantula SV, Robertson GP (2010) Targeting the MAPK pathway in melanoma: why some approaches succeed and other fail. Biochem Pharmacol 80:624–637CrossRefPubMedPubMedCentral Inamdar GS, Madhunapantula SV, Robertson GP (2010) Targeting the MAPK pathway in melanoma: why some approaches succeed and other fail. Biochem Pharmacol 80:624–637CrossRefPubMedPubMedCentral
go back to reference Innominato PF, Libbrecht L, van den Oord JJ (2001) Expression of neurotrophins and their receptors in pigment cell lesions of the skin. J Pathol 194:95–100CrossRefPubMed Innominato PF, Libbrecht L, van den Oord JJ (2001) Expression of neurotrophins and their receptors in pigment cell lesions of the skin. J Pathol 194:95–100CrossRefPubMed
go back to reference Inozume T et al (2005) Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients. Int J Cancer 114:283–290CrossRefPubMed Inozume T et al (2005) Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients. Int J Cancer 114:283–290CrossRefPubMed
go back to reference Jacquelot N et al (2016) Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma. J Clin Investig 126:921–937CrossRefPubMed Jacquelot N et al (2016) Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma. J Clin Investig 126:921–937CrossRefPubMed
go back to reference Jayakumar A, Rauvolfova J, Bao H, Fokt I, Skora S, Heimberger A, Priebe W (2013) Abstract 3251: Blockade of HIF-1 with a small molecule inhibitor WP1066 in melanoma. Cancer Res 73:3251–3251 Jayakumar A, Rauvolfova J, Bao H, Fokt I, Skora S, Heimberger A, Priebe W (2013) Abstract 3251: Blockade of HIF-1 with a small molecule inhibitor WP1066 in melanoma. Cancer Res 73:3251–3251
go back to reference Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010 CA: a cancer. J Clin 60:277–300 Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010 CA: a cancer. J Clin 60:277–300
go back to reference Jonsson G et al (2010) Gene expression profiling-based identification of molecular subtypes in stage IV Melanomas with different clinical outcome clinical cancer research an official. J Am Assoc Cancer Res 16:3356–3367 Jonsson G et al (2010) Gene expression profiling-based identification of molecular subtypes in stage IV Melanomas with different clinical outcome clinical cancer research an official. J Am Assoc Cancer Res 16:3356–3367
go back to reference Koh SS et al (2012) Differential gene expression profiling of primary cutaneous melanoma and sentinel lymph node metastases. Mod Pathol 25:828–837CrossRefPubMed Koh SS et al (2012) Differential gene expression profiling of primary cutaneous melanoma and sentinel lymph node metastases. Mod Pathol 25:828–837CrossRefPubMed
go back to reference Li T et al (2013) Identification of epithelial stromal interaction 1 as a novel effector downstream of Krüppel-like factor 8 in breast cancer invasion and metastasis. Oncogene 33:4746–4755CrossRefPubMedPubMedCentral Li T et al (2013) Identification of epithelial stromal interaction 1 as a novel effector downstream of Krüppel-like factor 8 in breast cancer invasion and metastasis. Oncogene 33:4746–4755CrossRefPubMedPubMedCentral
go back to reference Li FJ et al (2014) Emerging Roles for the FCRL Family Members in Lymphocyte Biology and Disease. Curr Top Microbiol Immunol 382:29–50PubMedPubMedCentral Li FJ et al (2014) Emerging Roles for the FCRL Family Members in Lymphocyte Biology and Disease. Curr Top Microbiol Immunol 382:29–50PubMedPubMedCentral
go back to reference Liu W, Peng Y, Tobin DJ (2013) A new 12-gene diagnostic biomarker signature of melanoma revealed by integrated microarray analysis PeerJ 1:e49 Liu W, Peng Y, Tobin DJ (2013) A new 12-gene diagnostic biomarker signature of melanoma revealed by integrated microarray analysis PeerJ 1:e49
go back to reference Lodolce J et al (2002) Interleukin-15 and the regulation of lymphoid homeostasis. Mol Immunol 39:537–544CrossRefPubMed Lodolce J et al (2002) Interleukin-15 and the regulation of lymphoid homeostasis. Mol Immunol 39:537–544CrossRefPubMed
go back to reference Macià A, Herreros J, Martí RM, Cantí C (2015) Calcium channel expression and applicability as targeted therapies in melanoma. Biomed Res Int 2015:587135CrossRefPubMedPubMedCentral Macià A, Herreros J, Martí RM, Cantí C (2015) Calcium channel expression and applicability as targeted therapies in melanoma. Biomed Res Int 2015:587135CrossRefPubMedPubMedCentral
go back to reference Maurer M, Somasundaram R, Herlyn M, Wagner SN (2012) Immunotargeting of tumor subpopulations in melanoma patients: A paradigm shift in therapy approaches. Oncoimmunology 1:1454–1456CrossRefPubMedPubMedCentral Maurer M, Somasundaram R, Herlyn M, Wagner SN (2012) Immunotargeting of tumor subpopulations in melanoma patients: A paradigm shift in therapy approaches. Oncoimmunology 1:1454–1456CrossRefPubMedPubMedCentral
go back to reference McGovern VJ et al (1973) The classification of malignant melanoma and its histologic reporting. Cancer 32:1446–1457 McGovern VJ et al (1973) The classification of malignant melanoma and its histologic reporting. Cancer 32:1446–1457
go back to reference Monti S, Tamayo P, Mesirov J, Golub T (2003) Consensus clustering: a resampling-based method for class discovery and visualization of gene expression microarray data. Mach Learn 52:91–118CrossRef Monti S, Tamayo P, Mesirov J, Golub T (2003) Consensus clustering: a resampling-based method for class discovery and visualization of gene expression microarray data. Mach Learn 52:91–118CrossRef
go back to reference Palmieri G (2012) Molecular classification of patients with cutaneous melanoma: a reality. J Mol Biomark Diagn 3:e110 Palmieri G (2012) Molecular classification of patients with cutaneous melanoma: a reality. J Mol Biomark Diagn 3:e110
go back to reference Payne AS, Cornelius LA (2002) The role of chemokines in melanoma tumor growth and metastasis. J Investig Dermatol 118:915–922CrossRefPubMed Payne AS, Cornelius LA (2002) The role of chemokines in melanoma tumor growth and metastasis. J Investig Dermatol 118:915–922CrossRefPubMed
go back to reference Rogers HW, Weinstock MA, Feldman SR, Coldiron BM (2015) Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US Population, 2012. Jama Dermatol 151:1081–1086CrossRefPubMed Rogers HW, Weinstock MA, Feldman SR, Coldiron BM (2015) Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US Population, 2012. Jama Dermatol 151:1081–1086CrossRefPubMed
go back to reference Rousseeuw PJ (1987) Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J Comput Appl Math 20:53–65CrossRef Rousseeuw PJ (1987) Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J Comput Appl Math 20:53–65CrossRef
go back to reference Scolyer RA, Long GV, Thompson JF (2011) Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care. Mol Oncol 5:124–136CrossRefPubMedPubMedCentral Scolyer RA, Long GV, Thompson JF (2011) Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care. Mol Oncol 5:124–136CrossRefPubMedPubMedCentral
go back to reference Stern RS (2010) Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol 146:279–282CrossRefPubMed Stern RS (2010) Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol 146:279–282CrossRefPubMed
go back to reference TCGA (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696CrossRef TCGA (2015) Genomic classification of cutaneous melanoma. Cell 161:1681–1696CrossRef
go back to reference Verreault M, Webb MS, Ramsay EC, Bally MB (2006) Gene silencing in the development of personalized cancer treatment: the targets, the agents and the delivery systems. Curr Gene Ther 6:505–533CrossRefPubMed Verreault M, Webb MS, Ramsay EC, Bally MB (2006) Gene silencing in the development of personalized cancer treatment: the targets, the agents and the delivery systems. Curr Gene Ther 6:505–533CrossRefPubMed
go back to reference Wang B et al (2014) Similarity network fusion for aggregating data types on a genomic scale. Nat Methods 11:333–337CrossRefPubMed Wang B et al (2014) Similarity network fusion for aggregating data types on a genomic scale. Nat Methods 11:333–337CrossRefPubMed
go back to reference Xu T et al (2017) CancerSubtypes: an R/Bioconductor package for molecular cancer subtype identification, validation, and visualization. Bioinformatics 33:3131–3133CrossRefPubMed Xu T et al (2017) CancerSubtypes: an R/Bioconductor package for molecular cancer subtype identification, validation, and visualization. Bioinformatics 33:3131–3133CrossRefPubMed
go back to reference Zhao Q, Shi X, Xie Y, Huang J, Shia B, Ma S (2015) Combining multidimensional genomic measurements for predicting cancer prognosis: observations from TCGA. Brief Bioinform 16:291–303CrossRefPubMed Zhao Q, Shi X, Xie Y, Huang J, Shia B, Ma S (2015) Combining multidimensional genomic measurements for predicting cancer prognosis: observations from TCGA. Brief Bioinform 16:291–303CrossRefPubMed
Metadata
Title
Molecular classification and subtype-specific characterization of skin cutaneous melanoma by aggregating multiple genomic platform data
Authors
Xiaofan Lu
Qianyuan Zhang
Yue Wang
Liya Zhang
Huiling Zhao
Chen Chen
Yaoyan Wang
Shengjie Liu
Tao Lu
Fei Wang
Fangrong Yan
Publication date
01-09-2018
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 9/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-018-2684-7

Other articles of this Issue 9/2018

Journal of Cancer Research and Clinical Oncology 9/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine