Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer
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Colorectal cancer is one of the most common cancers worldwide. We tested the hypothesis that differences in the expression of certain molecular markers of colon cancer may account for different clinical outcomes.
Tissue microarray technology was used to assay the expression of 17 biological markers [β-catenin, CD44v7, c-myc, cyclin D1, estrogen receptor β, mitogen-activated protein kinase/extracellular signal-regulated kinase, maspin, matrix metalloproteinase-7 (MMP7), p53, Pin1, peroxisome proliferators-activated receptor-gamma, survivin, T cell transcription factor 4 (TCF4), transforming growth factor beta receptor II (TGFβR II), TGFβ, TROP2, and Wnt] by immunohistochemistry in 620 colon cancer patients. The Cox proportional hazards regression model was applied to analyze the lifetime data, including time to death, time to recurrence, and time to liver metastasis.
All the markers were present at significantly higher expression levels in tumor specimens than in normal colonic specimens. Kaplan–Meier analysis showed that high expression of TROP2, MMP7, and survivin were related to decreased survival; TCF4 and TROP2 were related to disease recurrence; and CD44v7, cyclin D1, MMP7, p53, survivin, and TCF4 were related to liver metastasis. However, the results of the multivariate analysis only showed that expression of MMP7, survivin, and TROP2 were significant predictors of lower patient survival, while TROP2 and MMP7 were significantly related to disease recurrence and liver metastasis, respectively.
We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.
KeywordsColon carcinoma Prognosis Disease recurrence Liver metastasis
Supported by Grant No. 2004B3030102 from the Guangdong Science & Technology Planning Project.
- 23.Konstantinopoulos PA, Kominea A, Vandoros G, Sykiotis GP, Andricopoulos P, Varakis I et al (2003) Oestrogen receptor β (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon denocarcinoma paralleling the tumour’s dedifferentiation. Eur J Cancer 39:1251–1258PubMedCrossRefGoogle Scholar
- 27.Greene FL, Page DL, Fleming ID et al (2002) AJCC: cancer staging handbook: from the AJCC cancer staging manual, 6th edn. Springer, New YorkGoogle Scholar
- 28.Sobin LH, Wittekind C (eds) (2002) UICC: TNM classification of malignant tumours. Wiley, LondonGoogle Scholar
- 44.Rodel F, Hoffmann J, Grabenbauer GG, Papadopoulos T, Weiss C, Gunther K et al (2002) High survivin expression is associated with reduced apoptosis in rectal cancer and may predict disease-free survival after preoperative radiochemotherapy and surgical resection. Strahlenther Onkol 178:426–435PubMedCrossRefGoogle Scholar
- 54.Blanc-Brude OP, Mesri M, Wall NR, Plescia J, Dohi T, Altieri DC (2003) Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. Cancer Res 9:2683–2692Google Scholar