MicroRNA-9-5p-CDX2 Axis: A Useful Prognostic Biomarker for Patients with Stage II/III Colorectal Cancer.

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

doi:10.3390/cancers11121891

Aya Nishiuchi, Masazumi Sakaguchi + Show 13 more

Open Access

https://doi.org/10.3390/cancers11121891

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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.

Highlights

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide [1], and great efforts have been made to develop more effective treatment strategies, leading to improvements in the prognosis of patients with colorectal cancer (CRC)
We found that the prognosis of the caudal-type homeobox transcription factor 2 (CDX2)-negative group was significantly worse than that of the CDX2-positive group in our cohort of patients with stage II/III CRC
Lack of CDX2 Expression is Associated with Poor Prognosis of Stage II/ III CRC

Summary

Introduction

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide [1], and great efforts have been made to develop more effective treatment strategies, leading to improvements in the prognosis of patients with CRC. Surgery is the main treatment for patients with pathological stage II. CRC, whereas patients with stage III CRC are treated surgically followed by adjuvant chemotherapy [2]. The prognostic impact of these risk factors and benefits of adjuvant chemotherapy in these subgroups remain controversial [6]. While oxaliplatin and fluoropyrimidine-based chemotherapies are the standard adjuvant treatments for stage III CRC [7,8,9], these chemotherapy regimens often have little effect and can be severely toxic to some patients. A simple and reliable biomarker, useful for identifying subgroups of patients with aggressive stage II/III CRC, is needed as these patients are likely to benefit from adjuvant chemotherapy

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