原创力文档a minimal connected network of transcription factors regulated in human tumors and its application to the quest for universal cancer biomarkers转录因子调节的最小连接网络在人类肿瘤及其应用寻求普遍的癌症生物标记.pdfVIP
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a minimal connected network of transcription factors regulated in human tumors and its application to the quest for universal cancer biomarkers转录因子调节的最小连接网络在人类肿瘤及其应用寻求普遍的癌症生物标记
A Minimal Connected Network of Transcription Factors
Regulated in Human Tumors and Its Application to the
Quest for Universal Cancer Biomarkers
Ahmed Essaghir*, Jean-Baptiste Demoulin
´
de Duve institute, Universite Catholique de Louvain, Brussels, Belgium
Abstract
A universal cancer biomarker candidate for diagnosis is supposed to distinguish, within a broad range of tumors, between
healthy and diseased patients. Recently published studies have explored the universal usefulness of some biomarkers in
human tumors. In this study, we present an integrative approach to search for potential common cancer biomarkers. Using
the TFactS web-tool with a catalogue of experimentally established gene regulations, we could predict transcription factors
(TFs) regulated in 305 different human cancer cell lines covering a large panel of tumor types. We also identified
chromosomal regions having significant copy number variation (CNV) in these cell lines. Within the scope of TFactS
catalogue, 88 TFs whose activity status were explained by their gene expressions and CNVs were identified. Their minimal
connected network (MCN) of protein-protein interactions forms a significant module within the human curated TF
proteome. Functional analysis of the proteins included in this MCN revealed enrichment in cancer pathways as well as
inflammation. The ten most central proteins in MCN are TFs that trans-regulate 157 known genes encoding secreted and
transmembrane proteins. In publicly available collections of gene expression data from 8,525 patient tissues, 86 genes were
differentially regulated in cancer compared to inflammatory diseases and controls. From TCGA cancer gene expression data
sets, 50 genes were significantly associated to patient survival in at least one
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