Microrna-9-5p-CDX2 axis: A useful prognostic biomarker for patients with stage II/III colorectal cancer

Aya Nishiuchi, Shigeo Hisamori, Masazumi Sakaguchi, Keita Fukuyama, Nobuaki Hoshino, Yoshiro Itatani, Shusaku Honma, Hisatsugu Maekawa, Tatsuto Nishigori, Shigeru Tsunoda, Kazutaka Obama, Hiroyuki Miyoshi, Yohei Shimono, M. Mark Taketo, Yoshiharu Sakai

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Abstract

A lack of caudal-type homeobox transcription factor 2 (CDX2) protein expression has been proposed as a prognostic biomarker for colorectal cancer (CRC). However, the relationship between CDX2 levels and the survival of patients with stage II/III CRC along with the relationship between microRNAs (miRs) and CDX2 expression are unclear. Tissue samples were collected from patients with stage II/III CRC surgically treated at Kyoto University Hospital. CDX2 expression was semi-quantitatively evaluated by immunohistochemistry (IHC). The prognostic impacts of CDX2 expression on overall survival (OS) and relapse-free survival (RFS) were evaluated by multivariable statistical analysis. The expression of miRs regulating CDX2 expression and their prognostic impacts were analyzed using The Cancer Genome Atlas Program for CRC (TCGA-CRC). Eleven of 174 CRC tissues lacked CDX2 expression. The five-year OS and RFS rates of patients with CDX2-negative CRC were significantly lower than those of CDX2-positive patients. Multivariate analysis of clinicopathological features revealed that CDX2-negative status is an independent marker of poor prognosis in stage II/III CRC. miR-9-5p was shown to regulate CDX2 expression. TCGA-CRC analysis showed that high miR-9-5p expression was significantly associated with poor patient prognosis in stage II/III CRC. In conclusion, CDX2, the post-transcriptional target of microRNA-9-5p, is a useful prognostic biomarker in patients with stage II/III CRC.

Original languageEnglish
Article number1891
JournalCancers
Volume11
Issue number12
DOIs
Publication statusPublished - 12-2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Nishiuchi, A., Hisamori, S., Sakaguchi, M., Fukuyama, K., Hoshino, N., Itatani, Y., Honma, S., Maekawa, H., Nishigori, T., Tsunoda, S., Obama, K., Miyoshi, H., Shimono, Y., Mark Taketo, M., & Sakai, Y. (2019). Microrna-9-5p-CDX2 axis: A useful prognostic biomarker for patients with stage II/III colorectal cancer. Cancers, 11(12), [1891]. https://doi.org/10.3390/cancers11121891