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.