An integrated model of clinical information and gene expression for prediction of survival in ovarian cancer patients

被引:8
作者
Yang, Rendong
Xiong, Jie
Deng, Defeng
Wang, Yiren
Liu, Hequn
Jiang, Guli
Peng, Yangqin
Peng, Xiaoning [2 ]
Zeng, Xiaomin [1 ]
机构
[1] Cent S Univ, Xiangya Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Changsha, Hunan, Peoples R China
[2] Hunan Normal Univ, Coll Med, Dept Pathol & Pathophysiol, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
GROWTH-FACTOR RECEPTOR; REGULARIZATION PATHS; CDC7; KINASE; BIOINFORMATICS; MICRORNA-7; SIGNATURE; SERUM; PROGRESSION; PATTERNS; ORIGINS;
D O I
10.1016/j.trsl.2016.03.001
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Accumulating evidence shows that clinical factors alone are not adequate for predicting the survival of patients with ovarian cancer (OvCa), and many genes have been found to be associated with OvCa prognosis. The objective of this study was to develop a model that integrates clinical information and a gene signature to predict the survival durations of patients diagnosed with OvCa. We constructed mRNA and microRNA expression profiles and gathered the corresponding clinical data of 552 OvCa patients and 8 normal controls from The Cancer Genome Atlas. Using univariate Cox regression followed by a permutation test, elastic net-regulated Cox regression, and ridge regression, we generated a prognosis index consisting of 2 clinical variables, 7 protective mRNAs, 12 risky mRNAs, and 1 protective microRNA. The area under the curve of the receiver operating characteristic of the integrated clinical-and-gene model was 0.756, larger than that of the clinical-alone model (0.686) or the gene-alone model (0.703). OvCa patients in the high-risk group had a significantly shorter overall survival time compared with patients in the low-risk group (hazard ratio = 8.374, 95% confidence interval = 4.444-15.780, P = 4.90 x 10(-11), by the Wald test). The reliability of the gene signature was confirmed by a public external data set from the Gene Expression Omnibus. Our conclusions that we have identified an integrated clinical-and-gene model superior to the traditional clinical-alone model in ascertaining the survival prognosis of patients with OvCa. Our findings may prove valuable for improving the clinical management of OvCa.
引用
收藏
页码:84 / 95
页数:12
相关论文
共 61 条
[1]  
[Anonymous], 1949, EVALUATION CHEMOTHER
[2]  
[Anonymous], 2006, Journal of the Royal Statistical Society, Series B
[3]   COMPLEMENTARY DEOXYRIBONUCLEIC-ACID CLONING AND MOLECULAR CHARACTERIZATION OF AN ESTROGEN-DEPENDENT HUMAN OVIDUCTAL GLYCOPROTEIN [J].
ARIAS, EB ;
VERHAGE, HG ;
JAFFE, RC .
BIOLOGY OF REPRODUCTION, 1994, 51 (04) :685-694
[4]   Correlation Analysis of HOX, ErbB and IGFBP Family Gene Expression in Ovarian Cancer [J].
Bahrani-Mostafavi, Zahra ;
Tickle, Timothy L. ;
Zhang, Jian ;
Bennett, Kristen E. ;
Vachris, Judith C. ;
Spencer, Melanie D. ;
Mostafavi, M. Taghi ;
Tait, David L. .
CANCER INVESTIGATION, 2008, 26 (10) :990-998
[5]   Integrated genomic analyses of ovarian carcinoma [J].
Bell, D. ;
Berchuck, A. ;
Birrer, M. ;
Chien, J. ;
Cramer, D. W. ;
Dao, F. ;
Dhir, R. ;
DiSaia, P. ;
Gabra, H. ;
Glenn, P. ;
Godwin, A. K. ;
Gross, J. ;
Hartmann, L. ;
Huang, M. ;
Huntsman, D. G. ;
Iacocca, M. ;
Imielinski, M. ;
Kalloger, S. ;
Karlan, B. Y. ;
Levine, D. A. ;
Mills, G. B. ;
Morrison, C. ;
Mutch, D. ;
Olvera, N. ;
Orsulic, S. ;
Park, K. ;
Petrelli, N. ;
Rabeno, B. ;
Rader, J. S. ;
Sikic, B. I. ;
Smith-McCune, K. ;
Sood, A. K. ;
Bowtell, D. ;
Penny, R. ;
Testa, J. R. ;
Chang, K. ;
Dinh, H. H. ;
Drummond, J. A. ;
Fowler, G. ;
Gunaratne, P. ;
Hawes, A. C. ;
Kovar, C. L. ;
Lewis, L. R. ;
Morgan, M. B. ;
Newsham, I. F. ;
Santibanez, J. ;
Reid, J. G. ;
Trevino, L. R. ;
Wu, Y. -Q. ;
Wang, M. .
NATURE, 2011, 474 (7353) :609-615
[6]   Origins and molecular pathology of ovarian cancer [J].
Bell, DA .
MODERN PATHOLOGY, 2005, 18 :S19-S32
[7]   Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers [J].
Berchuck, A ;
Iversen, ES ;
Lancaster, JM ;
Pittman, J ;
Luo, JQ ;
Lee, P ;
Murphy, S ;
Dressman, HK ;
Febbo, PG ;
West, M ;
Nevins, JR ;
Marks, JR .
CLINICAL CANCER RESEARCH, 2005, 11 (10) :3686-3696
[8]   Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer [J].
Bernardi, Caroline C. ;
Ribeiro, Enilze de S. F. ;
Cavalli, Iglenir J. ;
Chautard-Freire-Maia, Eleidi A. ;
Souza, Ricardo L. R. .
CANCER GENETICS AND CYTOGENETICS, 2010, 197 (02) :158-165
[9]   A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer [J].
Bonome, Tomas ;
Levine, Douglas A. ;
Shih, Joanna ;
Randonovich, Mike ;
Pise-Masison, Cindy A. ;
Bogomolniy, Faina ;
Ozbun, Laurent ;
Brady, John ;
Barrett, J. Carl ;
Boyd, Jeff ;
Birrer, Michael J. .
CANCER RESEARCH, 2008, 68 (13) :5478-5486
[10]   Predicting survival from microarray data -: a comparative study [J].
Bovelstad, H. M. ;
Nygard, S. ;
Storvold, H. L. ;
Aldrin, M. ;
Borgan, O. ;
Frigessi, A. ;
Lingjaerde, O. C. .
BIOINFORMATICS, 2007, 23 (16) :2080-2087