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Mutations of p53 and K-ras correlate TF expression in human colorectal carcinomas: TF downregulation as a marker of poor prognosis

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Abstract

Background

Tissue factor (TF) is emphasized as the promising target in the future targeted therapy strategy for colorectal cancer (CRC). Recent evidence showed that TF expression is under the control of K-ras and p53. However, a comprehensive evaluation of TF expression, K-ras status, and p53 mutation has not been systematically analyzed. The aims of this study were to identify the percentages of positive TF in CRC patients; analyze the associations of TF expression, K-ras status, and p53 mutation; and evaluate the prognostic value of TF in CRC patients.

Methods

Ninety-six CRC samples were tested for TF expression, p53 mutation, and K-ras status by semiquantitative immunohistochemistry, Western blotting analysis, direct sequencing, and real-time quantitative PCR. Associations were sought with TF expression and clinical outcomes.

Results

TF expression was related to clinical stages, tumor differentiation, and tumor size. The positive proportions of TF expression on tumor cells and tumor vascular endothelial cells were 70% and 53% respectively in CRC patients. The positive proportion of TF co-expression on both cancer cells and tumor vascular endothelial cells was 40%, compared to an 83% total TF positive proportion in CRC patients. TF expression on CRC appeared to be increased with K-ras and/or p53 mutation(s). Disease-free survival and overall survival were significantly reduced in CRC patients with high TF expression.

Conclusions

TF may participate in both K-ras and p53 mutations involved in colorectal carcinogenesis and could be considered as a prognostic indicator for patients CRC.

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Acknowledgments

This project was supported by the program “The Implemented Research for an Experimentally Risk-genes Expression Prewarning Model in Personalized Medicine of Colorectal Cancer” (the program for substantial project incubation and new crossing subjects of Sun Yat-sen University, No.10ykjco2). We thank Dr. Daidre for offering English language editorial assistance.

Disclosure/conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Colorectal Surgery Department, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China

    Benqiang Rao, Jun Huang, Meijin Huang, Wanglin Li, Lei Wang & Jianping Wang

  2. Department of Radiation Oncology, Cancer Center, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Guangzhou, Guangdong, 510060, China

    Yuanhong Gao

  3. Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China

    Xiaoyan Gao

  4. Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China

    Jiayin Yao

  5. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China

    Jingping Wang

  6. Institute of Gastroenterology, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China

    Benqiang Rao, Xinhui Fu, Junxiao Zhang, Huanliang Liu, Lei Wang & Jianping Wang

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  1. Benqiang Rao
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  2. Yuanhong Gao
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  3. Jun Huang
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  5. Xinhui Fu
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  8. Jingping Wang
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  9. Wanglin Li
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  10. Junxiao Zhang
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  11. Huanliang Liu
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  12. Lei Wang
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  13. Jianping Wang
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Corresponding authors

Correspondence to Lei Wang or Jianping Wang.

Additional information

Benqiang Rao, Yuanhong Gao, and Lei Wang are the first authors.

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Rao, B., Gao, Y., Huang, J. et al. Mutations of p53 and K-ras correlate TF expression in human colorectal carcinomas: TF downregulation as a marker of poor prognosis. Int J Colorectal Dis 26, 593–601 (2011). https://doi.org/10.1007/s00384-011-1164-1

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  • DOI: https://doi.org/10.1007/s00384-011-1164-1

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