Skip to main content
Erschienen in: Tumor Biology 12/2016

05.10.2016 | Original Article

A new ten-gene risk fraction model serving as prognostic indicator for clinical outcome of multiple myeloma

verfasst von: Ai-Xin Hu, Zhi-Yong Huang, Ping Liu, Tian Xiang, Shi Yan, Li Zhang

Erschienen in: Tumor Biology | Ausgabe 12/2016

Einloggen, um Zugang zu erhalten

Abstract

Multiple myeloma (MM) is a kind of aggressive tumor prevalent with high heterogeneity. Abnormal expression of certain genes may lead to the occurrence and development of MM. Nowadays, it is not commonly seen in clinical research to predict the prognostic circumstances of patients with MM by multiple gene expression profiling method. Identification of potential genes in prognostic process could be beneficial for clinical management of MM. Therefore, we aimed to build a risk fraction model to screen out the prognostic indicator for clinical outcome of MM. Microarray data were downloaded from the Genome Expression Omnibus (GEO) datasets with accession numbers GSE24080 and GSE57317. A total of 279 samples were selected out randomly. Besides, a risk formula was constructed and verified in the dataset. Time-dependent receiver operating characteristic (ROC) curve was applied in evaluating the accurate prognostic conditions of patients. Finally, a ten genes model in the training dataset was found to be closely related to the survival condition of MM patients. Patients with MM were divided into two groups, high-risk and low-risk, by the expression of these ten genes, and significant statistical difference was found between the two groups. Furthermore, the result of multivariate cox regression and stratified analysis indicated that this model was independent of other clinical phenotypes. ROC curves also showed its feasibility to predict the survival status of MM patients. Our results demonstrated that the fraction risk model constructed by the selected ten genes could be used to predict survival status of multiple myeloma patients, which could also help in improvement of prognostic and therapeutic tool of MM.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B, Fonseca R, Stewart AK, Harousseau J-L, Dimopoulos M. Consensus recommendations for risk stratification in multiple myeloma: report of the international myeloma workshop consensus panel 2. Blood. 2011;117:4696–700.CrossRefPubMedPubMedCentral Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B, Fonseca R, Stewart AK, Harousseau J-L, Dimopoulos M. Consensus recommendations for risk stratification in multiple myeloma: report of the international myeloma workshop consensus panel 2. Blood. 2011;117:4696–700.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Decaux O, Lodé L, Magrangeas F, Charbonnel C, Gouraud W, Jézéquel P, Attal M, Harousseau J-L, Moreau P, Bataille R. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the intergroupe francophone du myelome. J Clin Oncol. 2008;26:4798–805.CrossRefPubMed Decaux O, Lodé L, Magrangeas F, Charbonnel C, Gouraud W, Jézéquel P, Attal M, Harousseau J-L, Moreau P, Bataille R. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the intergroupe francophone du myelome. J Clin Oncol. 2008;26:4798–805.CrossRefPubMed
3.
Zurück zum Zitat Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.CrossRefPubMedPubMedCentral Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Tran B, Dancey JE, Kamel-Reid S, McPherson JD, Bedard PL, Brown AM, Zhang T, Shaw P, Onetto N, Stein L, Hudson TJ, Neel BG, Siu LL. Cancer genomics: technology, discovery, and translation. Cancer genomics: technology, discovery, and translation. J Clin Oncol. 2012;30(6):647–60. Tran B, Dancey JE, Kamel-Reid S, McPherson JD, Bedard PL, Brown AM, Zhang T, Shaw P, Onetto N, Stein L, Hudson TJ, Neel BG, Siu LL. Cancer genomics: technology, discovery, and translation. Cancer genomics: technology, discovery, and translation. J Clin Oncol. 2012;30(6):647–60.
5.
Zurück zum Zitat Arpino G, Generali D, Sapino A, Del Matro L, Frassoldati A, de Laurentis M, Pronzato P, Mustacchi G, Cazzaniga M, De Placido S. Gene expression profiling in breast cancer: a clinical perspective. Breast. 2013;22:109–20.CrossRefPubMed Arpino G, Generali D, Sapino A, Del Matro L, Frassoldati A, de Laurentis M, Pronzato P, Mustacchi G, Cazzaniga M, De Placido S. Gene expression profiling in breast cancer: a clinical perspective. Breast. 2013;22:109–20.CrossRefPubMed
6.
Zurück zum Zitat Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, Beaumont C, Clark-Langone KM, Yoshizawa CN, Lee M. Validation study of a quantitative multigene reverse transcriptase–polymerase chain reaction assay for assessment of recurrence risk in patients with stage ii colon cancer. J Clin Oncol. 2011;29:4611–9.CrossRefPubMed Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, Beaumont C, Clark-Langone KM, Yoshizawa CN, Lee M. Validation study of a quantitative multigene reverse transcriptase–polymerase chain reaction assay for assessment of recurrence risk in patients with stage ii colon cancer. J Clin Oncol. 2011;29:4611–9.CrossRefPubMed
7.
Zurück zum Zitat Choudhury AD, Eeles R, Freedland SJ, Isaacs WB, Pomerantz MM, Schalken JA, Tammela TL, Visakorpi T. The role of genetic markers in the management of prostate cancer. Eur Urol. 2012;62:577–87.CrossRefPubMed Choudhury AD, Eeles R, Freedland SJ, Isaacs WB, Pomerantz MM, Schalken JA, Tammela TL, Visakorpi T. The role of genetic markers in the management of prostate cancer. Eur Urol. 2012;62:577–87.CrossRefPubMed
8.
Zurück zum Zitat Alizadeh AA, Gentles AJ, Alencar AJ, Liu CL, Kohrt HE, Houot R, Goldstein MJ, Zhao S, Natkunam Y, Advani RH. Prediction of survival in diffuse large b-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood. 2011;118:1350–8.CrossRefPubMedPubMedCentral Alizadeh AA, Gentles AJ, Alencar AJ, Liu CL, Kohrt HE, Houot R, Goldstein MJ, Zhao S, Natkunam Y, Advani RH. Prediction of survival in diffuse large b-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood. 2011;118:1350–8.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Consortium M. The microarray quality control (maqc)-ii study of common practices for the development and validation of microarray-based predictive models. Nat Biotechnol. 2010;28:827–38.CrossRef Consortium M. The microarray quality control (maqc)-ii study of common practices for the development and validation of microarray-based predictive models. Nat Biotechnol. 2010;28:827–38.CrossRef
10.
Zurück zum Zitat Gevaert O, Xu J, Hoang CD, Leung AN, Xu Y, Quon A, Rubin DL, Napel S, Plevritis SK. Non–small cell lung cancer: identifying prognostic imaging biomarkers by leveraging public gene expression microarray data—methods and preliminary results. Radiology. 2012;264:387–96.CrossRefPubMedPubMedCentral Gevaert O, Xu J, Hoang CD, Leung AN, Xu Y, Quon A, Rubin DL, Napel S, Plevritis SK. Non–small cell lung cancer: identifying prognostic imaging biomarkers by leveraging public gene expression microarray data—methods and preliminary results. Radiology. 2012;264:387–96.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Harbron C, Chang K-M, South MC. Refplus: an r package extending the rma algorithm. Bioinformatics. 2007;23:2493–4.CrossRefPubMed Harbron C, Chang K-M, South MC. Refplus: an r package extending the rma algorithm. Bioinformatics. 2007;23:2493–4.CrossRefPubMed
12.
Zurück zum Zitat Proaño A, Aragón RE, Proaño JL. Escore z: Fenton 2013. Atualizacão de dez anos. J Pediatr. 2014;90:426.CrossRef Proaño A, Aragón RE, Proaño JL. Escore z: Fenton 2013. Atualizacão de dez anos. J Pediatr. 2014;90:426.CrossRef
14.
Zurück zum Zitat O’Quigley J, Moreau T. Cox’s regression model: computing a goodness of fit statistic. Comput Methods Prog Biomed. 1986;22:253–6.CrossRef O’Quigley J, Moreau T. Cox’s regression model: computing a goodness of fit statistic. Comput Methods Prog Biomed. 1986;22:253–6.CrossRef
15.
Zurück zum Zitat Pedersen PA, Kristensen FB. The Danish medical statistics and Danish practical research. Ugeskr Laeger. 1990;152:828–9.PubMed Pedersen PA, Kristensen FB. The Danish medical statistics and Danish practical research. Ugeskr Laeger. 1990;152:828–9.PubMed
16.
Zurück zum Zitat Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. 1975;50:29–40.PubMed Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc. 1975;50:29–40.PubMed
17.
Zurück zum Zitat Bataille R, Boccadoro M, Klein B, Durie B, Pileri A. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood. 1992;80:733–7.PubMed Bataille R, Boccadoro M, Klein B, Durie B, Pileri A. C-reactive protein and beta-2 microglobulin produce a simple and powerful myeloma staging system. Blood. 1992;80:733–7.PubMed
18.
Zurück zum Zitat Dimopoulos MA, Barlogie B, Smith TL, Alexanian R. High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma. Ann Intern Med. 1991;115:931–5.CrossRefPubMed Dimopoulos MA, Barlogie B, Smith TL, Alexanian R. High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma. Ann Intern Med. 1991;115:931–5.CrossRefPubMed
19.
Zurück zum Zitat Seidel C, Hjertner Ø, Abildgaard N, Heickendorff L, Hjorth M, Westin J, Nielsen JL, Hjorth-Hansen H, Waage A, Sundan A. Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood. 2001;98:2269–71.CrossRefPubMed Seidel C, Hjertner Ø, Abildgaard N, Heickendorff L, Hjorth M, Westin J, Nielsen JL, Hjorth-Hansen H, Waage A, Sundan A. Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood. 2001;98:2269–71.CrossRefPubMed
20.
Zurück zum Zitat Heagerty PJ, Lumley T, Pepe MS. Time-dependent roc curves for censored survival data and a diagnostic marker. Biometrics. 2000;56:337–44.CrossRefPubMed Heagerty PJ, Lumley T, Pepe MS. Time-dependent roc curves for censored survival data and a diagnostic marker. Biometrics. 2000;56:337–44.CrossRefPubMed
Metadaten
Titel
A new ten-gene risk fraction model serving as prognostic indicator for clinical outcome of multiple myeloma
verfasst von
Ai-Xin Hu
Zhi-Yong Huang
Ping Liu
Tian Xiang
Shi Yan
Li Zhang
Publikationsdatum
05.10.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5449-4

Weitere Artikel der Ausgabe 12/2016

Tumor Biology 12/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.