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Overexpression of PTGIS Could Predict Liver Metastasis and is Correlated with Poor Prognosis in Colon Cancer Patients

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Pathology & Oncology Research

Abstract

The purpose of this study was to evaluate the predictive ability of PTGIS for liver metastasis. Protein expression of PTGIS was analyzed on tissue microarray consisting of 117 CRC cases with liver metastasis (M1) and 104 cases of CRC without liver metastasis at least 5 years after resection of primary CRC (M0) by immunohistochemistry. Expression of PTGIS in 147 of 221 of primary lesions exhibited positive staining. Moreover, the PTGIS expression was significantly higher in CRC-M1 than CRC-M0 group. More importantly, the 87% (20/23) heterochronous metastatic cases showed positive staining for PTGIS. Collecting the primary and liver metastatic tumor samples from the same colon cancer patients, we tested the expression of PTGIS and revealed that the expression level of PTGIS in the hepatic metastases was noticeably higher than in the matched primary colon cancer tissues from the same patient in 9 out of 16 cases examined. Logistic regression analysis indicated that the expression of PTGIS and lymph node involvement were risk factors in colon cancer liver metastasis independent of the other variables. In leave-one-out validation model, the combination of PTGIS and lymph node involvement yielded the 89.7% satisfactory sensitivity and 83% specificity for detection of hepatic metastasis. Kaplan–Meier survival analysis revealed a correlation between higher PTGIS expression levels and shorter overall survival times. In conclusion, our results suggest that PTGIS combined with lymph node involvement may be used as accurate predictors of liver metastasis in colorectal cancer.

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References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  2. McMillan DC, McArdle CS (2007) Epidemiology of colorectal liver metastases. Surg Oncol 16:3–5

    Article  PubMed  Google Scholar 

  3. Forman BM, Chen J, Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ. Proc Natl Acad Sci U S A 94:4312–4317

    Article  PubMed  CAS  Google Scholar 

  4. Park BH, Vogelstein B, Kinzler KW (2001) Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci U S A 98:2598–2603

    Article  PubMed  CAS  Google Scholar 

  5. Lim H, Gupta RA, Ma W-g et al (1999) Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARδ. Genes Dev 13:1561–1574

    Article  PubMed  CAS  Google Scholar 

  6. Cutler NS, Graves-Deal R, LaFleur BJ et al (2003) Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells. Cancer Res 63:1748–1751

    PubMed  CAS  Google Scholar 

  7. Frigola J, Munoz M, Clark SJ, Moreno V, Capella G, Peinado MA (2005) Hypermethylation of the prostacyclin synthase (PTGIS) promoter is a frequent event in colorectal cancer and associated with aneuploidy. Oncogene 24:7320–7326

    Article  PubMed  CAS  Google Scholar 

  8. Lambert LA, Colacchio TA, Barth RJ (2000) Interval hepatic resection of colorectal metastases improves patient selection*. Curr Surg 57:504

    Article  PubMed  Google Scholar 

  9. Kan T, Shimada Y, Sato F et al (2004) Prediction of lymph node metastasis with use of artificial neural networks based on gene expression profiles in esophageal squamous cell carcinoma. Ann Surg Oncol 11:1070–1078

    Article  PubMed  Google Scholar 

  10. Hu H, Sun L, Guo C et al (2009) Tumor cell-microenvironment interaction models coupled with clinical validation reveal CCL2 and SNCG as two predictors of colorectal cancer hepatic metastasis. Clin Cancer Res 15:5485–5493

    Article  PubMed  CAS  Google Scholar 

  11. Wang D, DuBois RN (2007) Measurement of eicosanoids in cancer tissues. Methods Enzymol 433:27–50

    Article  PubMed  CAS  Google Scholar 

  12. He T-C, Chan TA, Vogelstein B, Kinzler KW (1999) PPAR’ is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99:335–345

    Article  PubMed  CAS  Google Scholar 

  13. Munemitsu S, Albert I, Souza B, Rubinfeld B, Polakis P (1995) Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Sci 92:3046–3050

    Article  PubMed  CAS  Google Scholar 

  14. Galaup A, Cazes A, Le Jan S et al (2006) Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci 103:18721–18726

    Article  PubMed  CAS  Google Scholar 

  15. Vane J, Corin RE (2003) Prostacyclin: a vascular mediator. Eur J Vasc Endovasc Surg 26:571–578

    Article  PubMed  CAS  Google Scholar 

  16. Buchanan FG, Chang W, Sheng H, Shao J, Morrow JD, DuBois RN (2004) Up-regulation of the enzymes involved in prostacyclin synthesis via Ras induces vascular endothelial growth factor. Gastroenterology 127:1391–1400

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China

    Sun Lichao, Lv Fang & Ran Yuliang

  2. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China

    Peng Liang

  3. Department of abdominal surgical oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, People’s Republic of China

    Guo Chunguang

  4. Department of Cell and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China

    Yang Zhihua

Authors
  1. Sun Lichao
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  2. Peng Liang
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  3. Guo Chunguang
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  4. Lv Fang
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  5. Yang Zhihua
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  6. Ran Yuliang
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Corresponding authors

Correspondence to Yang Zhihua or Ran Yuliang.

Additional information

Lichao Sun and Liang Peng contributed equally to this work.

Supported by grant from

The National Key Basic Research Program of China. (2009CB521804)

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Lichao, S., Liang, P., Chunguang, G. et al. Overexpression of PTGIS Could Predict Liver Metastasis and is Correlated with Poor Prognosis in Colon Cancer Patients. Pathol. Oncol. Res. 18, 563–569 (2012). https://doi.org/10.1007/s12253-011-9478-4

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  • DOI: https://doi.org/10.1007/s12253-011-9478-4

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