Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma

Shilpa Jain, Shashideep Singhal, Franto Francis, Cristina Hajdu, Jin Hua Wang, Arief Suriawinata, Yin Quan Wang, Miao Zhang, Elizabeth H. Weinshel, Fritz Francois, Zhi Heng Pei, Peng Lee, Ru Liang Xu

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archiival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβR. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1γ was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFβR was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1γ overexpression were significantly higher in stage III than in stage I and II CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome.

Original languageEnglish (US)
Pages (from-to)3994-4000
Number of pages7
JournalWorld Journal of Gastroenterology
Volume17
Issue number35
DOIs
StatePublished - Sep 21 2011

Keywords

  • Colorectal cancer
  • Smad4
  • Transcriptional intermediary factor 1 gamma
  • Transforming growth factor-beta signaling pathway

ASJC Scopus subject areas

  • Gastroenterology

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    Jain, S., Singhal, S., Francis, F., Hajdu, C., Wang, J. H., Suriawinata, A., Wang, Y. Q., Zhang, M., Weinshel, E. H., Francois, F., Pei, Z. H., Lee, P., & Xu, R. L. (2011). Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma. World Journal of Gastroenterology, 17(35), 3994-4000. https://doi.org/10.3748/wjg.v17.i35.3994