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2015 ; 10
(9
): e0137171
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Discovery of a Novel Immune Gene Signature with Profound Prognostic Value in
Colorectal Cancer: A Model of Cooperativity Disorientation Created in the Process
from Development to Cancer
#MMPMID26325386
An N
; Shi X
; Zhang Y
; Lv N
; Feng L
; Di X
; Han N
; Wang G
; Cheng S
; Zhang K
PLoS One
2015[]; 10
(9
): e0137171
PMID26325386
show ga
Immune response-related genes play a major role in colorectal carcinogenesis by
mediating inflammation or immune-surveillance evasion. Although remarkable
progress has been made to investigate the underlying mechanism, the understanding
of the complicated carcinogenesis process was enormously hindered by large-scale
tumor heterogeneity. Development and carcinogenesis share striking similarities
in their cellular behavior and underlying molecular mechanisms. The association
between embryonic development and carcinogenesis makes embryonic development a
viable reference model for studying cancer thereby circumventing the potentially
misleading complexity of tumor heterogeneity. Here we proposed that the immune
genes, responsible for intra-immune cooperativity disorientation (defined in this
study as disruption of developmental expression correlation patterns during
carcinogenesis), probably contain untapped prognostic resource of colorectal
cancer. In this study, we determined the mRNA expression profile of 137 human
biopsy samples, including samples from different stages of human colonic
development, colorectal precancerous progression and colorectal cancer samples,
among which 60 were also used to generate miRNA expression profile. We originally
established Spearman correlation transition model to quantify the cooperativity
disorientation associated with the transition from normal to precancerous to
cancer tissue, in conjunction with miRNA-mRNA regulatory network and machine
learning algorithm to identify genes with prognostic value. Finally, a 12-gene
signature was extracted, whose prognostic value was evaluated using Kaplan-Meier
survival analysis in five independent datasets. Using the log-rank test, the
12-gene signature was closely related to overall survival in four datasets
(GSE17536, n = 177, p = 0.0054; GSE17537, n = 55, p = 0.0039; GSE39582, n = 562,
p = 0.13; GSE39084, n = 70, p = 0.11), and significantly associated with
disease-free survival in four datasets (GSE17536, n = 177, p = 0.0018; GSE17537,
n = 55, p = 0.016; GSE39582, n = 557, p = 4.4e-05; GSE14333, n = 226, p = 0.032).
Cox regression analysis confirmed that the 12-gene signature was an independent
factor in predicting colorectal cancer patient's overall survival (hazard ratio:
1.759; 95% confidence interval: 1.126-2.746; p = 0.013], as well as disease-free
survival (hazard ratio: 2.116; 95% confidence interval: 1.324-3.380; p = 0.002).