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Method of Prognosing Cancers Verfahren Zur Prognose Von Krebsarten Procédé De Prognostic Des Cancers

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Method of Prognosing Cancers Verfahren Zur Prognose Von Krebsarten Procédé De Prognostic Des Cancers (19) TZZ Z _T (11) EP 2 295 602 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 33/574 (2006.01) C12Q 1/68 (2006.01) 11.07.2012 Bulletin 2012/28 (21) Application number: 10178350.4 (22) Date of filing: 26.07.2006 (54) Method of prognosing cancers Verfahren zur Prognose von Krebsarten Procédé de prognostic des cancers (84) Designated Contracting States: • KIHARA C ET AL: "Prediction of sensitivity of AT BE BG CH CY CZ DE DK EE ES FI FR GB GR esophageal tumors to adjuvant chemotherapy by HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI cDNA microarray analysis of gene-expression SK TR profiles", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, (30) Priority: 27.07.2005 US 703263 P BALTIMORE, MD, US, vol. 61, no. 17, September 2001 (2001-09), pages 6474-6479, XP002960719, (43) Date of publication of application: ISSN: 0008-5472 16.03.2011 Bulletin 2011/11 • PORTE H ET AL: "Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in (62) Document number(s) of the earlier application(s) in human esophageal carcinoma: implications for accordance with Art. 76 EPC: prognosis.", CLINICAL CANCER RESEARCH : 06782211.4 / 1 907 582 AN OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH. JUN (73) Proprietor: Oncotherapy Science, Inc. 1998, vol. 4, no. 6, June 1998 (1998-06), pages Kawasaki-shi 1375-1382, XP002407525, ISSN: 1078-0432 Kanagawa 213-0012 (JP) • "Affimetrix GeneChip Human Genome U133 Array Set HG-U133A", GEO, 11 March 2002 (72) Inventors: (2002-03-11), XP002254749, • Nakamura, Yusuke • WIGLE DENNIS A ET AL: "Molecular profiling of Tokyo 1138654 (JP) non-small cell lung cancer and correlation with • Daigo, Yataro disease-free survival", CANCER RESEARCH, Tokyo 1138654 (JP) AMERICAN ASSOCIATION FOR CANCER • Nakatsuru, Shuichi REREARCH, US, vol. 62, no. 11, 1 June 2002 Kawasaki-shi Kanagawa 213-0012 (2002-06-01), pages 3005-3008, XP002271233, (JP) ISSN: 0008-5472 • BEER D G ET AL: "Gene-expression profiles (74) Representative: Vossius & Partner predict survival of patients with lung Siebertstrasse 4 adenocarcinoma", NATURE MEDICINE, NATURE 81675 München (DE) PUBLISHING GROUP, NEW YORK, NY, US, vol. 8, no. 8, 1 August 2002 (2002-08-01), pages (56) References cited: 816-824, XP002279225, ISSN: 1078-8956 WO-A1-01/74405 WO-A2-2005/033343 • ZHOU JIN ET AL: "Gene expression profiles at different stages of human esophageal squamous cell carcinoma", WORLD JOURNAL OF GASTROENTEROLOGY, XX, XX, vol. 9, no. 1, January 2003 (2003-01), pages 9-15, XP002334878, ISSN: 1007-9327 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 295 602 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 295 602 B1 • KIMCHI ERIK T ET AL: "Progression of Barrett’s • YAMABUKI TAKUMI ET AL: "Genome-wide gene metaplasiatoadenocarcinomaisassociatedwith expression profile analysis of esophageal the suppression of the transcriptional programs squamous cell carcinomas.", INTERNATIONAL of epidermal differentiation.", CANCER JOURNAL OF ONCOLOGY. JUN 2006, vol. 28, no. RESEARCH. 15 APR 2005, vol. 65, no. 8, 15 April 6, June 2006 (2006-06), pages 1375-1384, 2005 (2005-04-15) , pages 3146-3154, XP009074902, ISSN: 1019-6439 XP002407523, ISSN: 0008-5472 • TOMOKI MAKINO ET AL: "Dickkopf-1 Expression • KAN TAKATSUGU ET AL: "Prediction of lymph as a Marker for Predicting Clinical Outcome in node metastasis with use of artificial neural Esophageal Squamous Cell Carcinoma", networks based on gene expression profiles in ANNALS OF SURGICAL ONCOLOGY, esophageal squamous cell carcinoma.", SPRINGER-VERLAG, NE, vol. 16, no. 7, 30 April ANNALS OF SURGICAL ONCOLOGY : THE 2009 (2009-04-30) , pages 2058-2064, OFFICIAL JOURNAL OF THE SOCIETY OF XP019668260, ISSN: 1534-4681 SURGICAL ONCOLOGY. DEC 2004, vol. 11, no. • DARLAVOIX T ET AL: "Altered expression of 12, December 2004 (2004-12), pages 1070-1078, CD44 and DKK1 in the progression of Barrettâ s XP002407524, ISSN: 1068-9265 esophagus to esophageal adenocarcinoma", VIRCHOWS ARCHIV, SPRINGER, BERLIN, DE, vol. 454, no. 6, 25 April 2009 (2009-04-25), pages 629-637, XP019715724, ISSN: 1432-2307 2 EP 2 295 602 B1 Description FIELD OF THE INVENTION 5 [0001] The present invention relates to methods for providing a prognosis of esophageal squamous-cell carcinoma (ESCC), and non-small cell lung cancer (NSCLC). BACKGROUND OF THE INVENTION 10 [0002] Lung cancer is the leading cause of cancer-related death in the world. Despite some advances in early detection and recent improvements in its treatment, the prognosis of the patients with lung cancer remains poor (Parkin et al, Lancet Oncol. 2001 Sep;2(9):533-43). On the other hand, esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignant tumors in the gastrointestinal carcinoma family. The majority of esophageal cancers are advanced at the time of presentation and diagnosis, rendering cure unlikely, especially by surgery alone (Shimada et al., Surgery. 15 2003;133(5):486-94). In spite of the use of modern surgical techniques combined with multi-treatment modalities, such as radiotherapy and chemotherapy, the over all 5-year survival rate remains 40-60% (Tamoto et al., Clin Cancer Res. 2004;10(11):3629-38) while that of lung cancer is only 15 % (Parkin et al, Lancet Oncol. 2001 Sep;2(9):533-43). In fact, it is reported that recurrent ESCC had developed in almost half of the patients who underwent an apparently curative resection, at a median follow up of 37.3 months (Mariette et al., Cancer. 2003; 97(7):1616-23). Consequently, much 20 research effort has been directed towards studies of adjuvant chemotherapy and chemoradiation, particularly in defining the best regimens from the standpoint of efficacy and minimal toxicity and in an attempt to predict response. However, developments in neoadjuvant and adjuvant therapies have led to mixed conclusions. Collectively, past studies have not shown an optimal neoadjuvant or adjuvant regimen in terms of survival benefit. Therefore, there is an urgent need for novel diagnostic tools for early detection of cancer and molecular-targeted therapies involving small-molecule and 25 antibody-based approaches. [0003] In that vein, several tumor markers are used for diagnosis and follow-up of patients with ESCC, for example, SCC (squamous-cell carcinoma antigens), CEA (carcinoembryonic antigen), and CYFRA 21-1. Recently, serum MK (midkine), CD147, MMP-2 (matrix metalloproteinase-2), MMP-26 and MMP-9 in patients with ESCC was reported to be associated with poor prognosis (Shimada et al., Cancer Sci. 2003;94(7):628-32; Kawaguchi et al., Cancer. 2000;89(7): 30 1413-7; Ishibashi et al., Cancer. 2004;101(9):1994-2000; Yamamoto et al., Carcinogenesis. 2004;25(12):2353-60). However, at present, no specific tumor marker is clinically useful for detection of ESCC at an early and potentially curative stage. Therefore, new diagnostic and therapeutic strategies such as development of molecular-targeted agents and antibodies as well as cancer vaccines, are urgently needed. Several tumor markers, such as proGPP, NSE, cytokeratin 19-fragment (CYFRA 21-1), squamous-cell carcinoma antigen (SCC), and carcinoembryonic antigen (CEA) have been 35 increased in the circulation of lung cancer patients (Castaldo G, et al., J Clin Oncol. 1997 Nov;15(11):3388-93.; Peck et al., Cancer Res. 1998 Jul 1;58(13):2761-5.; Salerno et al., Chest. 1998 Jun; 113(6):1526-32.), while SCC, CEA, and CYFRA 21-1 for ESCC, are used in clinic for diagnosis as well as in follow-up of the patients (Shimada et al., Surgery. 2003 May;133(5):486-94, Kawaguchi et al., Cancer. 2000 Oct 1;89(7):1413-7). In NSCLC patients, the sensitivity of CEA was 25% in squamous-cell carcinoma and 50% in adenocarcinoma, whereas, the sensitivity of SCC was 30% in 40 squamous-cell carcinoma (Rastel et al., Eur J Cancer. 1994;30A(5):601-6). The sensitivity of CYFRA 21-1 was 57% in squamous-cell carcinoma and 27% in adenocarcinoma (Rastel et al., Eur J Cancer. 1994;30A(5):601-6). Reportedly, the positive rate of serum SCC in patients with ESCC was 18% in stage I, 22% in stage II, 34% in stage III, and 37% in stage IV. The incidence of CEA positivity in patients with stage IV ESCC was only 16%. Although CEA was not a prognostic factor, SCC was shown to be an independent prognostic factor to pTNM factors by using multivariate analysis 45 (Shimada et al., Surgery. 2003 May; 133(5):486-94). These facts indicate that no tumor marker has been proven to be useful for detection of lung cancer and ESCC at potentially curative stage, and a limited number of practical prognostic marker is presently available for selection of treatment modalities for individual patients. [0004] Analysis of gene-expression profiles on cDNA microarray enables the comprehensive analysis of gene ex- pression profiles in cancer cells, and some studies describing such transcription profiles have been reported. For example, 50 with regard to ESCC, several studies reported gene expression profiles of human ESCC that are candidates as diagnostic markers or therapeutic targets (Luo et al., Oncogene. 2004 ;23(6):1291-9; Kihara et al., Cancer Res. 2001;61(17): 6474-9;, Tamoto et al., Clin Cancer Res. 2004;10(11):3629-38). However, all of the previous studies in human ESCC involved bulk tumor tissues and, since ESCC contains various types of cells, such as mesenchymal cells and inflammatory cells, fail to reflect accurate expressional changes during esophageal carcinogenesis (Nishida et al., Cancer Res.
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