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Combination of Haptoglobin and Osteopontin Could Predict Colorectal Cancer Hepatic Metastasis

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

Abstract

Purpose

This study aimed to identify novel molecular markers for the early detection of colorectal cancer liver metastasis.

Methods

Genes related to hepatic metastasis were screened from the Oncomine database. The candidate markers were tested by immunohistochemistry, and their predictive accuracy was assessed by the cross-validation method and an independent test set.

Results

We got three datasets containing 2,973 genes that were highly expressed in primary colon cancer tissues compared with non-metastatic colon cancer tissues and identified 7 candidate molecules for immunohistochemical validation. A total of 213 colorectal cancer samples were randomly divided into a training set (113 cases) and a blind testing set (100 cases). In the training set, immunohistochemical analysis showed that HP, OPN, and PTGIS expression were significantly higher in the hepatic metastasis group than in the non-metastasis group. Logistic regression analysis showed that HP and OPN levels in primary tumors and lymph node metastasis status were the only significant (P < 0.05) parameters for detecting liver metastasis. The predictive accuracy of markers was assessed by the cross-validation method and an independent test set. In leave-one-out cross-validation, the two markers combined with clinicopathologic features resulted in 91.2% sensitivity and 96.4% specificity for hepatic metastasis detection. In an independent test set, the combination achieved 94.5% sensitivity and 88.9% specificity for predicting the hepatic metastasis of colorectal cancer.

Conclusions

Our results suggest that combined HP and OPN expression levels are significantly related to liver metastasis and prognosis, and, if this is validated, they could be used as accurate predictors of liver metastasis in colorectal cancer.

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Acknowledgment

This study was supported by The National Key Basic Research Program of China (2009CB521804 and 2010CB933902) and by PUMC&CAMS Funds for Young Scholar.

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Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

    Lichao Sun MD, Lv Fang PhD, Xuan Zhao MS, Lixin Sun MS & Yuliang Ran PhD

  2. Department of Hematology and Oncology, Children’s Hospital of Soochow University, Suzhou, China

    Jian Pan PhD

  3. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, People’s Republic of China

    Liang Peng PhD

  4. Department of Cell and Molecular Biology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

    Zhihua Yang BS

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  1. Lichao Sun MD
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  2. Jian Pan PhD
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  4. Lv Fang PhD
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  5. Xuan Zhao MS
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  6. Lixin Sun MS
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  7. Zhihua Yang BS
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Correspondence to Zhihua Yang BS or Yuliang Ran PhD.

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Sun, L., Pan, J., Peng, L. et al. Combination of Haptoglobin and Osteopontin Could Predict Colorectal Cancer Hepatic Metastasis. Ann Surg Oncol 19, 2411–2419 (2012). https://doi.org/10.1245/s10434-011-2177-2

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  • DOI: https://doi.org/10.1245/s10434-011-2177-2

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