title: Genes involved in the transition from normal epithelium to intraepithelial neoplasia are associated with colorectal cancer patient survival.
abstract: Whether the heterogeneity in tumor cell morphology and behavior is the consequence of a progressive accumulation of genetic alterations or an intrinsic property of cancer-initiating cells established at initiation remains controversial. The hypothesis of biological predetermination in human cancer was proposed many years ago and states that the biological potency of cancer cells is predestinated in the precancerous stage. The present study aimed to investigate whether the aberrant molecular events occurring in initial cancer stages could eventually influence colorectal cancer (CRC) progression. We analyzed the mRNA and miRNA expression profiles of colorectal normal mucosa, low-grade intraepithelial neoplasia (LIN), high-grade intraepithelial neoplasia (HIN), and adenocarcinoma tissues. Compared with the transitions from LIN to HIN to invasive carcinoma, the transition from normal epithelium to LIN appeared to be associated with greater changes in the number and expression levels of mRNAs and miRNAs, with a differential expression of 2322 mRNAs and 71 miRNAs detected. Utilizing these early molecular changes, a miRNA-hub network analysis showed that 166 genes were identified as targets regulated by 30 miRNAs. Among these genes, a 55-gene signature regulated by 5 miRNAs was shown to be associated with overall survival or disease-free survival in three independent sample sets. Thus, the molecular changes in the transcriptome associated with the transition from normal to intraepithelial neoplasm may influence CRC progression.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Shi
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bangrong
authors.initials: B
authors.lastname: Cao
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Lin
authors.initials: L
authors.lastname: Feng
authors.forename: Xuebing
authors.initials: X
authors.lastname: Di
authors.forename: Naijun
authors.initials: N
authors.lastname: Han
authors.forename: Chenghua
authors.initials: C
authors.lastname: Luo
authors.forename: Guiqi
authors.initials: G
authors.lastname: Wang
authors.forename: Shujun
authors.initials: S
authors.lastname: Cheng
authors.forename: Kaitai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002278:Carcinoma in Situ / Q000235:genetics* / Q000401:mortality*; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D052138:Genes, Neoplasm / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D015995:Prevalence; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers