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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Translational Research and Biomarkers

Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer

Authors: Masami Ueda, MD, Tomohiro Iguchi, MD, PhD, Sho Nambara, MD, Tomoko Saito, MD, Hisateru Komatsu, MD, Shotaro Sakimura, MD, Hidenari Hirata, MD, Ryutaro Uchi, MD, Yuki Takano, MD, Yoshiaki Shinden, MD, Hidetoshi Eguchi, MD, PhD, Takaaki Masuda, MD, PhD, Keishi Sugimachi, MD, PhD, Hirofumi Yamamoto, MD, PhD, Yuichiro Doki, MD, PhD, Masaki Mori, MD, PhD, FACS, Koshi Mimori, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2015

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Abstract

Background

RNA polymerase 1 transcription termination factor (TTF1) mediates the transcription of ribosomal RNA (rRNA). In the current study, we investigated the clinical and biological significance of the TTF1 gene in colorectal cancer (CRC).

Methods

The expression of TTF1 messenger RNA (mRNA) in tumor and normal tissues from 136 patients with CRC was examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We also performed in vitro cell proliferation and migration assays in TTF1-expressing CRC cells. The biological role of TTF1 in CRC was further elucidated using gene set enrichment analysis (GSEA) with CRC samples.

Results

TTF1 expression was significantly higher in tumor tissues than in corresponding normal tissues (p = 0.016). In clinicopathological analysis, the high-TTF1 expression group showed a higher incidence of liver metastasis and lymphatic invasion than the low-TTF1 expression group (p < 0.05), and tended to have more frequent venous invasion than the low-TTF1 expression group. Furthermore, the high-TTF1 expression group had a significantly poorer prognosis than the low-TTF1 expression group (p = 0.011). Moreover, overexpression of TTF1 enhanced the proliferation and migration capacity of CRC cells in vitro. GSEA revealed that TTF1 was significantly associated with the RAS and MYC pathways, and this observation was confirmed in samples from 136 patients with CRC.

Conclusion

TTF1 was involved in cancer progression via the RAS and MYC pathways in CRC, suggesting that TTF1 may be a prognostic indicator and therapeutic target in CRC.
Appendix
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Metadata
Title
Overexpression of Transcription Termination Factor 1 is Associated with a Poor Prognosis in Patients with Colorectal Cancer
Authors
Masami Ueda, MD
Tomohiro Iguchi, MD, PhD
Sho Nambara, MD
Tomoko Saito, MD
Hisateru Komatsu, MD
Shotaro Sakimura, MD
Hidenari Hirata, MD
Ryutaro Uchi, MD
Yuki Takano, MD
Yoshiaki Shinden, MD
Hidetoshi Eguchi, MD, PhD
Takaaki Masuda, MD, PhD
Keishi Sugimachi, MD, PhD
Hirofumi Yamamoto, MD, PhD
Yuichiro Doki, MD, PhD
Masaki Mori, MD, PhD, FACS
Koshi Mimori, MD, PhD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4652-7

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