Urinary peptide panel for prognostic assessment of bladder cancer relapse

被引:12
作者
Krochmal, Magdalena [1 ]
van Kessel, Kim E. M. [2 ,3 ]
Zwarthoff, Ellen C. [2 ]
Belczacka, Iwona [1 ]
Pejchinovski, Martin [1 ]
Vlahou, Antonia [4 ]
Mischak, Harald [1 ]
Frantzi, Maria [1 ]
机构
[1] Mosaiques Diagnost GmbH, Hannover, Germany
[2] Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands
[3] Erasmus MC, Dept Urol, Erasmus MC Canc Inst, Rotterdam, Netherlands
[4] Acad Athens BRFAA, Div Biotechnol, Biomed Res Fdn, Athens, Greece
基金
欧盟地平线“2020”;
关键词
INVASIVE UROTHELIAL CARCINOMA; EORTC RISK TABLES; EAU GUIDELINES; BIOMARKER DISCOVERY; PROGRESSION; VALIDATION; RECURRENCE; PROTEINS; PROTEOME; MODEL;
D O I
10.1038/s41598-019-44129-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Non-invasive tools stratifying bladder cancer (BC) patients according to the risk of relapse are urgently needed to guide clinical intervention. As a follow-up to the previously published study on CE-MS-based urinary biomarkers for BC detection and recurrence monitoring, we expanded the investigation towards BC patients with longitudinal data. Profiling datasets of BC patients with follow-up information regarding the relapse status were investigated. The peptidomics dataset (n = 98) was split into training and test set. Cox regression was utilized for feature selection in the training set. Investigation of the entire training set at the single peptide level revealed 36 peptides being strong independent prognostic markers of disease relapse. Those features were further integrated into a Random Forest-based model evaluating the risk of relapse for BC patients. Performance of the model was assessed in the test cohort, showing high significance in BC relapse prognosis [HR =5.76, p-value =0.0001, c-index =0.64]. Urinary peptide profiles integrated into a prognostic model allow for quantitative risk assessment of BC relapse highlighting the need for its incorporation in prospective studies to establish its value in the clinical management of BC.
引用
收藏
页数:10
相关论文
共 49 条
[21]   Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma [J].
Hedegaard, Jakob ;
Lamy, Philippe ;
Nordentoft, Iver ;
Algaba, Ferran ;
Hoyer, Soren ;
Ulhoi, Benedicte Parm ;
Vang, Soren ;
Reinert, Thomas ;
Hermann, Gregers G. ;
Mogensen, Karin ;
Thomsen, Mathilde Borg Houlberg ;
Nielsen, Morten Muhlig ;
Marquez, Mirari ;
Segersten, Ulrika ;
Aine, Mattias ;
Hoglund, Mattias ;
Birkenkamp-Demtroder, Karin ;
Fristrup, Niels ;
Borre, Michael ;
Hartmann, Arndt ;
Stoehr, Robert ;
Wach, Sven ;
Keck, Bastian ;
Seitz, Anna Katharina ;
Nawroth, Roman ;
Maurer, Tobias ;
Tulic, Cane ;
Simic, Tatjana ;
Junker, Kerstin ;
Horstmann, Marcus ;
Harving, Niels ;
Petersen, Astrid Christine ;
Luz Calle, M. ;
Steyerberg, Ewout W. ;
Beukers, Willemien ;
van Kessel, Kim E. M. ;
Jensen, Jorgen Bjerggaard ;
Pedersen, Jakob Skou ;
Malmstrom, Per-Uno ;
Malats, Nuria ;
Real, Francisco X. ;
Zwarthoff, Ellen C. ;
Orntoft, Torben Falck ;
Dyrskjot, Lars .
CANCER CELL, 2016, 30 (01) :27-42
[22]   Update on Immunohistochemistry for the Diagnosis of Lung Cancer [J].
Inamura, Kentaro .
CANCERS, 2018, 10 (03)
[23]   Quantitative Urinary Proteome Analysis for Biomarker Evaluation in Chronic Kidney Disease [J].
Jantos-Siwy, Justyna ;
Schiffer, Eric ;
Brand, Korbinian ;
Schumann, Gerhard ;
Rossing, Kasper ;
Delles, Christian ;
Mischak, Harald ;
Metzger, Jochen .
JOURNAL OF PROTEOME RESEARCH, 2009, 8 (01) :268-281
[24]   Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity [J].
Knowles, Margaret A. ;
Hurst, Carolyn D. .
NATURE REVIEWS CANCER, 2015, 15 (01) :25-41
[25]   Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention [J].
Latosinska, Agnieszka ;
Mokou, Marika ;
Makridakis, Manousos ;
Mullen, William ;
Zoidakis, Jerome ;
Lygirou, Vasiliki ;
Frantzi, Maria ;
Katafigiotis, Ioannis ;
Stravodimos, Konstantinos ;
Hupe, Marie C. ;
Dobrzynski, Maciej ;
Kolch, Walter ;
Merseburger, Axel S. ;
Mischak, Harald ;
Roubelakis, Maria G. ;
Vlahou, Antonia .
ONCOTARGET, 2017, 8 (41) :69435-69455
[26]   FOXO1 down-regulation is associated with worse outcome in bladder cancer and adds significant prognostic information to p53 overexpression [J].
Lloreta, Josep ;
Font-Tello, Alba ;
Juanpere, Nuria ;
Frances, Albert ;
Lorenzo, Marta ;
Nonell, Lara ;
de Muga, Silvia ;
Vazquez, Ivonne ;
Cecchini, Lluis ;
Hernandez-Llodra, Silvia .
HUMAN PATHOLOGY, 2017, 62 :222-231
[27]   Preoperative neutrophil-lymphocyte ratio and fibrinogen level in patients distinguish between muscle-invasive bladder cancer and non-muscle-invasive bladder cancer [J].
Ma, Chengquan ;
Lu, Bingxin ;
Diao, Chengwen ;
Zhao, Kun ;
Wang, Xinpeng ;
Ma, Baojing ;
Lu, Baojian ;
Sun, Erlin .
ONCOTARGETS AND THERAPY, 2016, 9 :4917-4922
[28]   CD99: A Cell Surface Protein with an Oncojanus Role in Tumors [J].
Manara, Maria Cristina ;
Pasello, Michela ;
Scotlandi, Katia .
GENES, 2018, 9 (03)
[29]   The case for well-conducted experiments to validate statistical protocols for 2D gels: different pre-processing = different lists of significant proteins [J].
Meleth, S ;
Deshane, J ;
Kim, H .
BMC BIOTECHNOLOGY, 2005, 5 (1)
[30]   Mass spectrometry for the detection of differentially expressed proteins: a comparison of surface-enhanced laser desorption/ionization and capillary electrophoresis/mass spectrometry [J].
Neuhoff, NV ;
Kaiser, T ;
Wittke, S ;
Krebs, R ;
Pitt, A ;
Burchard, A ;
Sundmacher, A ;
Schlegelberger, B ;
Kolch, W ;
Mischak, H .
RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2004, 18 (02) :149-156