Differential expression in normal-adenoma-carcinoma sequence suggests complex molecular carcinogenesis in colon

Oncol Rep. 2006 Oct;16(4):747-54.

Abstract

The majority of colon cancers develop from pre-existing adenomas. We analyzed the expression profiles in the sequence of normal colon crypts, adenomas and early-stage carcinomas using microdissected cells from tubular adenomas with foci of malignant transformation. Differentially expressed genes were detected between normal-adenoma and adenoma-carcinoma, and were grouped according to the patterns of expression changes in the sequence. Down-regulated genes in the sequence included PLA2G2A, TSPAN1, PDCD4, FCGBP, AATK, EPLIN, FABP1, AGR2, MTUS1, TSC1, galectin 4 and MT1F. PLA2G2A has been shown to suppress colon tumorigenesis in mice, but the pathobiological role in humans has been controversial. Our data showed continuous down-regulation of PLA2G2A in the sequence supporting an implication in human colon cancer. Tumor suppressor and/ or proapoptotic activities have also been reported in other genes. Up-regulated genes included ribosomal proteins, IER3 and TPR. TGF-beta2 and matrix metalloproteinase 23B were up-regulated in carcinoma but not in adenoma, supporting the pathobiological roles in malignant transformation. Differentially expressed genes partly coincided with those in the adenoma-carcinoma sequence of the stomach, which was published previously, suggesting a partial overlap between the adenoma-carcinoma sequences of the colon and stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / pathology
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Colon / metabolism
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Disease Progression
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis