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2017 ; 8
(44
): 77515-77526
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Gene network inherent in genomic big data improves the accuracy of prognostic
prediction for cancer patients
#MMPMID29100405
Kim YH
; Jeong DC
; Pak K
; Goh TS
; Lee CS
; Han ME
; Kim JY
; Liangwen L
; Kim CD
; Jang JY
; Cha W
; Oh SO
Oncotarget
2017[Sep]; 8
(44
): 77515-77526
PMID29100405
show ga
Accurate prediction of prognosis is critical for therapeutic decisions regarding
cancer patients. Many previously developed prognostic scoring systems have
limitations in reflecting recent progress in the field of cancer biology such as
microarray, next-generation sequencing, and signaling pathways. To develop a new
prognostic scoring system for cancer patients, we used mRNA expression and
clinical data in various independent breast cancer cohorts (n=1214) from the
Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene
Expression Omnibus (GEO). A new prognostic score that reflects gene network
inherent in genomic big data was calculated using Network-Regularized
high-dimensional Cox-regression (Net-score). We compared its discriminatory power
with those of two previously used statistical methods: stepwise variable
selection via univariate Cox regression (Uni-score) and Cox regression via
Elastic net (Enet-score). The Net scoring system showed better discriminatory
power in prediction of disease-specific survival (DSS) than other statistical
methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC
validation cohorts) when accuracy was examined by log-rank test. Notably,
comparison of C-index and AUC values in receiver operating characteristic
analysis at 5 years showed fewer differences between training and validation
cohorts with the Net scoring system than other statistical methods, suggesting
minimal overfitting. The Net-based scoring system also successfully predicted
prognosis in various independent GEO cohorts with high discriminatory power. In
conclusion, the Net-based scoring system showed better discriminative power than
previous statistical methods in prognostic prediction for breast cancer patients.
This new system will mark a new era in prognosis prediction for cancer patients.