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Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown.

Materials and Methods

We used Western blotting to examine Msi-1 protein expression in 8 cases of primary colon cancer lesions and paired normal colonic mucosa. Msi-1 expression and clinicopathological significance were determined by immunohistochemical staining in a tissue microarray (TMA) containing 203 cases of primary colon cancer paired with noncancerous tissue and 66 lymph node metastasis (LNM) tissues. RNAi was used to analyze the biological function of Msi-1 in vitro.

Results

LNM tissue exhibited a striking increase in Msi-1 expression when compared with primary colon cancer and adjacent normal mucosa (87.9% vs. 64.5% vs. 16.7%, P < .001). Overexpression of Msi-1 was associated with higher clinical stage, T stage, lymph node metastasis, presence of distant metastasis, and Ki-67 positivity. Msi-1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) (HR 5.4; P < .001) and poorer overall survival (OS) (HR 3.8; P < .001). Msi-1 silencing significantly inhibited proliferation ability and attenuated the migration and invasion activity of colon cancer cells.

Conclusions

Our study provides the basis to explore the use of Msi-1 as a novel prognostic biomarker in colon cancer patients. Aberrant overexpression of Msi-1 during metastasis of colon cancer also suggests that it is a potential therapeutic target.

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Acknowledgment

This study was supported by the fund: National High Technology Research and Development Program (“863” Program) of China (No. 2007AA022003); Public Scientific Research Platform of Hospital of Grade A at the Tertiary Level of Shanghai (No. SHDC12007704); Outstanding Medical Academic Leader of Shanghai Municipality (No. LJ06024).

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Authors and Affiliations

  1. Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, People’s Republic of China

    Dawei Li MD, PhD, Dongwang Yan MD, PhD, Fei Huang MD & Zhihai Peng MD, PhD

  2. Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China

    Xiao Peng MD

  3. Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, People’s Republic of China

    Huamei Tang MD

  4. Department of Colorectal Surgery, Affiliated Hospital of Ningxia Medical University, Ningxia, People’s Republic of China

    Yinxue Yang MD, PhD

Authors
  1. Dawei Li MD, PhD
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  2. Xiao Peng MD
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  3. Dongwang Yan MD, PhD
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  4. Huamei Tang MD
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  5. Fei Huang MD
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  6. Yinxue Yang MD, PhD
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  7. Zhihai Peng MD, PhD
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Corresponding authors

Correspondence to Yinxue Yang MD, PhD or Zhihai Peng MD, PhD.

Additional information

D. Li, X. Peng, and D. Yan contributed equally to this study.

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Li, D., Peng, X., Yan, D. et al. Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer. Ann Surg Oncol 18, 2074–2083 (2011). https://doi.org/10.1245/s10434-011-1567-9

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  • DOI: https://doi.org/10.1245/s10434-011-1567-9

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