Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions

被引：53

作者：

Alcala, Nicolas ^{[1
]}

Mangiante, Lise ^{[1
]}

Le-Stang, Nolwenn ^{[2
]}

Gustafson, Corinne E. ^{[3
,4
]}

Boyault, Sandrine ^{[5
]}

Damiola, Francesca ^{[2
]}

Alcala, Karine ^{[1
]}

Brevet, Marie ^{[6
]}

Thivolet-Bejui, Francoise ^{[6
]}

Blanc-Fournier, Cecile ^{[7
]}

Le Rochais, Jean-Philippe ^{[7
]}

Planchard, Gaetane ^{[7
]}

Rousseau, Nathalie ^{[7
]}

Damotte, Diane ^{[8
]}

Pairon, Jean Claude ^{[9
]}

Copin, Marie Christine ^{[10
]}

Scherpereel, Arnaud ^{[10
]}

Wasielewski, Eric ^{[10
]}

Wicquart, Laurence ^{[10
]}

Lacomme, Stephanie ^{[11
]}

Vignaud, Jean-Michel ^{[11
]}

Ancelin, Gaspard ^{[12
]}

Girard, Cecile ^{[12
]}

Sagan, Christine ^{[12
]}

Bonnetaud, Christelle ^{[13
]}

Hofman, Veronique ^{[13
]}

Hofman, Paul ^{[13
]}

Mouroux, Jerome ^{[13
]}

de Montpreville, Vincent Thomas ^{[14
]}

Clermont-Taranchon, Estelle ^{[15
]}

Mazieres, Julien ^{[15
]}

Rouquette, Isabelle ^{[15
]}

Begueret, Hugues ^{[16
]}

Blay, Jean-Yves ^{[17
,18
]}

Lantuejoul, Sylvie ^{[2
,19
]}

Bueno, Raphael ^{[3
,4
]}

Caux, Christophe ^{[20
]}

Girard, Nicolas ^{[18
,21
,22
,23
]}

McKay, James D. ^{[1
]}

Foll, Matthieu ^{[1
]}

Galateau-Salle, Francoise ^{[2
]}

Fernandez-Cuesta, Lynnette ^{[1
]}

机构：

[1] Int Agcy Res Canc IARC WHO, Sect Genet, Lyon, France

[2] CLB, Dept Pathol, Lyon, France

[3] Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA

[4] Harvard Med Sch, Boston, MA 02115 USA

[5] CRCL, Translat Res & Innovat Platform, Lyon, France

[6] Univ Claude Bernard Lyon 1, Pathol Inst, Hosp Civils Lyon, Lyon, France

[7] CHU Caen, Caen Univ Hosp, Caen, France

[8] Paris Ctr Univ Hosp, Paris, France

[9] Ctr Hosp Intercommunal Creteil, Paris, France

[10] Lille Univ Hosp, Lille, France

[11] Nancy Univ Hosp, Nancy, France

[12] Nantes Univ Hosp, Nantes, France

[13] Nice Univ Hosp, Nice, France

[14] Marie Lannelongue Hosp, Le Plessis Robinson, France

[15] Toulouse Univ Hosp, Toulouse, France

[16] Bordeaux Univ Hosp, Bordeaux, France

[17] CLB, Dept Med Oncol, Lyon, France

[18] European Reference Network ENR EURACAN, Lyon, France

[19] Univ Grenoble Alpes, Grenoble, France

[20] CRCL, Dept Immun Virus & Inflammat, Lyon, France

[21] Univ Lyon 1, Lyon, France

[22] INSERM, U932, Paris, France

[23] Inst Curie, Paris, France

来源：

EBIOMEDICINE | 2019年 / 48卷

关键词：

Pleural mesothelioma; Immunotherapy; Angiogenesis; MESOMICS project; French MESOBANK; SURVIVAL; CANCER;

D O I：

10.1016/j.ebiom.2019.09.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options. Methods: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples. Findings: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" badprognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and proangiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDLI, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series. Interpretation: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response. (C) 2019 World Health Organization; licensee Elsevier.

引用

页码：191 / 202

页数：12

共 46 条

[1] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[2]

[Anonymous], CLASS TUM LUNG PLEUR

[3] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[4] Survival Analysis Part III: Multivariate data analysis - choosing a model and assessing its adequacy and fit [J].

Bradburn, MJ ;

Clark, TG ;

Love, SB ;

Altman, DG .

BRITISH JOURNAL OF CANCER, 2003, 89 (04) :605-611

[5]

Bueno R., 2016, NAT GENET

[6] Consensus Report of the 2015 Weinman International Conference on Mesothelioma [J].

Carbone, Michele ;

Kanodia, Shreya ;

Chao, Ann ;

Miller, Aubrey ;

Wali, Anil ;

Weissman, David ;

Adjei, Alex ;

Baumann, Francine ;

Boffetta, Paolo ;

Buck, Brenda ;

de Perrot, Marc ;

Dogan, A. Umran ;

Gavett, Steve ;

Gualtieri, Alessandro ;

Hassan, Raffit ;

Hesdorffer, Mary ;

Hirsch, Fred R. ;

Larson, David ;

Mao, Weimin ;

Masten, Scott ;

Pass, Harvey I. ;

Peto, Julian ;

Pira, Enrico ;

Steele, Ian ;

Tsao, Anne ;

Woodard, Gavitt Alida ;

Yang, Haining ;

Malik, Shakun .

JOURNAL OF THORACIC ONCOLOGY, 2016, 11 (08) :1246-1262

[7] Estimation of time-dependent area under the ROC curve for long-term risk prediction [J].

Chambless, Lloyd E. ;

Diao, Guoqing .

STATISTICS IN MEDICINE, 2006, 25 (20) :3474-3486

[8] Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas [J].

Combaz-Lair, Christelle ;

Galateau-Salle, Francoise ;

McLeer-Florin, Anne ;

Le Stang, Nolwenn ;

David-Boudet, Laurence ;

Duruisseaux, Mickael ;

Ferretti, Gilbert R. ;

Brambilla, Elisabeth ;

Lebecque, Serge ;

Lantuejoul, Sylvie .

HUMAN PATHOLOGY, 2016, 52 :9-18

[9] Treat it or Leave it: Immuno-Oncology in Mesothelioma Observed by the Eyes of Argus [J].

de Gooijer, Cornedine J. ;

Baas, Paul .

JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (11) :1619-1622

[10] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

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