Twist, a novel oncogene, is upregulated in pancreatic cancer: clinical implication of Twist expression in pancreatic juice

Int J Cancer. 2007 Apr 15;120(8):1634-40. doi: 10.1002/ijc.22295.

Abstract

Despite evidence that Twist, a highly conserved basic helix-loop-helix transcription factor, is a novel oncogene, there are no reports describing Twist expression in pancreatic cancer. Intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia (PanIN) are precursor lesions of pancreatic cancer. To clarify involvement of Twist expression in pancreatic cancer, we used quantitative reverse transcription-polymerase chain reaction and examined Twist expression in pancreatic cancer, IPMN, and non-neoplastic pancreas using bulk tissues (11 cancers, 18 IPMNs, and 15 non-neoplastic pancreata), microdissected cells (cancer from 22 sections, IPMN from 19 sections, PanIN from 6 sections, and pancreatitis-affected epithelial cells from 14 sections), and pancreatic juice (16 from cancer, 28 from IPMN, and 17 from pancreatitis). Twist expression differed significantly between cancer and IPMN bulk tissues (p < 0.0001) but not between cancer and non-neoplastic tissues. Twist expressions differed significantly between microdissected cancer cells, IPMN cells, and pancreatitis-affected cells (all comparisons, p < 0.017). PanIN cells expressed significantly lower levels of Twist than did IDC cells (p = 0.016). Twist expression differed significantly between cancer and IPMN juice samples (p = 0.0002) but not between cancer and pancreatitis juice samples. Receiver operation characteristic curve analyses revealed that measurement of Twist was more useful for discriminating cancer from IPMN than from chronic pancreatitis (p = 0.009). Our results suggest that Twist is involved in tumor progression of pancreatic cancer and that measurement of Twist in pancreatic juice may be useful to differentiate pancreatic cancer from nonmalignant neoplasms such as IPMN.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism
  • Cells, Cultured
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Nuclear Proteins / genetics*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Juice / physiology*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatitis / genetics
  • Pancreatitis / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Twist-Related Protein 1 / genetics*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Twist-Related Protein 1