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POSTER PRESENTATION Open Access Previously defined 53 immune gene panel predicts melanoma survival using The Cancer Genome Atlas (TCGA) Robyn Gartrell 1* , Qian Yingzhi 2 , Lopez Gonzalo 3 , Fu Yichun 4 , White-Stern Ashley 4 , Bansal Mukesh 3 , Sivendran Shanthi 5 , Califano Andrea 3 , Chang Rui 6 , Saenger Yvonne 1 From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015) National Harbor, MD, USA. 4-8 November 2015 Background Our laboratory has discovered a 53-immune gene panel predictive of survival in patients with stage II-III mela- noma [1]. Validation is planned using tissues from a multi-institutional cooperative group study. We tested the 53-immune gene panel using publicly available data for melanoma from The Cancer Genome Atlas (TCGA). Methods TCGA dataset for melanoma (n=407) was screened to determine two extreme groups of patients alive at least 4 years (n=67) and dead within 2 years from diagnosis (n=59). Genome wide differential expression analysis was performed between the two groups to study our prognos- tic signature. We used gene set enrichment analysis (GSEA) to evaluate the activation status of the 53 gene panel as well as multiple immune lineage specific gene sets[2]. We used PAM clustering algorithm to define two groups based on the expression data of the 53 genes and performed survival analysis on the unsupervised patient clusters. Results Prognostic relevance of the 53 gene panel was tested using supervised and unsupervised approaches. First, the prognostic signature shows striking GSEA results (p=2.24e-5) with activation of 51 of the 53 immune genes in good prognosis patients, indicated by a right shift in the enrichment score (Figure 1). GSEA of immune lineage specific gene sets 2 is shown in Figure 2. Using an unsupervised approach we studied the 53 gene panel across the whole population of melanoma cases with clinical and expression data reported in the TCGA (n=336). The generated heat map shows two distinct clusters of expression (Figure 3). A Kaplan Meier curve shows overall survival at 10 years in Cluster 1: 31.4 % and Cluster 2: 45.6%, (p =0.00261). Conclusions Using publically available data from TCGA we tested the 53-immune gene panel using supervised and unsu- pervised approaches, showing that 51 of the 53 genes are predictive of survival. This shows that the immune genes may be operative in different stages of melanoma. We propose using this panel to evaluate the effect of immunotherapy across melanoma cohorts, and have begun this analysis. We will also be evaluating the use of the 53 immune genes and the specific immune gene subsets on other cancer populations. Authorsdetails 1 Columbia University/New York Presbyterian, New York, NY, USA. 2 Columbia University, New York, NY, USA. 3 Department of Systems Biology at Columbia University, New York, NY, USA. 4 Columbia University College of Physicians of Surgeons, New York, NY, USA. 5 Lancaster General Health, Hummelstown, PA, USA. 6 Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA. Published: 4 November 2015 References 1. Sivendran S, et al: Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease. JID 2014, 134:2202-11. 2. Bindea G, et al: Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013, 39:782-95. 1 Columbia University/New York Presbyterian, New York, NY, USA Full list of author information is available at the end of the article Gartrell et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P283 http://www.immunotherapyofcancer.org/content/3/S2/P283 © 2015 Gartrell et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Page 1: POSTER PRESENTATION Open Access Previously defined 53 … · 2017. 8. 26. · POSTER PRESENTATION Open Access Previously defined 53 immune gene panel predicts melanoma survival using

POSTER PRESENTATION Open Access

Previously defined 53 immune gene panelpredicts melanoma survival using The CancerGenome Atlas (TCGA)Robyn Gartrell1*, Qian Yingzhi2, Lopez Gonzalo3, Fu Yichun4, White-Stern Ashley4, Bansal Mukesh3,Sivendran Shanthi5, Califano Andrea3, Chang Rui6, Saenger Yvonne1

From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC2015)National Harbor, MD, USA. 4-8 November 2015

BackgroundOur laboratory has discovered a 53-immune gene panelpredictive of survival in patients with stage II-III mela-noma [1]. Validation is planned using tissues from amulti-institutional cooperative group study. We testedthe 53-immune gene panel using publicly available datafor melanoma from The Cancer Genome Atlas (TCGA).

MethodsTCGA dataset for melanoma (n=407) was screened todetermine two extreme groups of patients – alive at least4 years (n=67) and dead within 2 years from diagnosis(n=59). Genome wide differential expression analysis wasperformed between the two groups to study our prognos-tic signature. We used gene set enrichment analysis(GSEA) to evaluate the activation status of the 53 genepanel as well as multiple immune lineage specific genesets[2]. We used PAM clustering algorithm to define twogroups based on the expression data of the 53 genes andperformed survival analysis on the unsupervised patientclusters.

ResultsPrognostic relevance of the 53 gene panel was testedusing supervised and unsupervised approaches. First, theprognostic signature shows striking GSEA results(p=2.24e-5) with activation of 51 of the 53 immunegenes in good prognosis patients, indicated by a rightshift in the enrichment score (Figure 1). GSEA ofimmune lineage specific gene sets2 is shown in Figure 2.

Using an unsupervised approach we studied the 53 genepanel across the whole population of melanoma caseswith clinical and expression data reported in the TCGA(n=336). The generated heat map shows two distinctclusters of expression (Figure 3). A Kaplan Meier curveshows overall survival at 10 years in Cluster 1: 31.4 %and Cluster 2: 45.6%, (p =0.00261).

ConclusionsUsing publically available data from TCGA we testedthe 53-immune gene panel using supervised and unsu-pervised approaches, showing that 51 of the 53 genesare predictive of survival. This shows that the immunegenes may be operative in different stages of melanoma.We propose using this panel to evaluate the effect ofimmunotherapy across melanoma cohorts, and havebegun this analysis. We will also be evaluating the useof the 53 immune genes and the specific immune genesubsets on other cancer populations.

Authors’ details1Columbia University/New York Presbyterian, New York, NY, USA. 2ColumbiaUniversity, New York, NY, USA. 3Department of Systems Biology at ColumbiaUniversity, New York, NY, USA. 4Columbia University College of Physicians ofSurgeons, New York, NY, USA. 5Lancaster General Health, Hummelstown, PA,USA. 6Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.

Published: 4 November 2015

References1. Sivendran S, et al: Dissection of immune gene networks in primary

melanoma tumors critical for antitumor surveillance of patients withstage II-III resectable disease. JID 2014, 134:2202-11.

2. Bindea G, et al: Spatiotemporal dynamics of intratumoral immune cellsreveal the immune landscape in human cancer. Immunity 2013,39:782-95.

1Columbia University/New York Presbyterian, New York, NY, USAFull list of author information is available at the end of the article

Gartrell et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P283http://www.immunotherapyofcancer.org/content/3/S2/P283

© 2015 Gartrell et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided theoriginal work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Gartrell et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P283http://www.immunotherapyofcancer.org/content/3/S2/P283

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Page 3: POSTER PRESENTATION Open Access Previously defined 53 … · 2017. 8. 26. · POSTER PRESENTATION Open Access Previously defined 53 immune gene panel predicts melanoma survival using

doi:10.1186/2051-1426-3-S2-P283Cite this article as: Gartrell et al.: Previously defined 53 immune genepanel predicts melanoma survival using The Cancer Genome Atlas(TCGA). Journal for ImmunoTherapy of Cancer 2015 3(Suppl 2):P283.

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Gartrell et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P283http://www.immunotherapyofcancer.org/content/3/S2/P283

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