Clinical prognostic value of combined analysis of Aldh1, Survivin,and EpCAM expression in colorectal cancer |
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Authors: | I J Goossens-Beumer E C M Zeestraten A Benard T Christen M S Reimers R Keijzer C F M Sier G J Liefers H Morreau H Putter A L Vahrmeijer C J H van de Velde P J K Kuppen |
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Affiliation: | 1.Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands;2.Department of Pathology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands;3.Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands |
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Abstract: | Background: Tumour aggressiveness might be related to the degree of main cancer hallmark acquirement of tumour cells, reflected by expression levels of specific biomarkers. We investigated the expression of Aldh1, Survivin, and EpCAM, together reflecting main cancer hallmarks, in relation to clinical outcome of colorectal cancer (CRC) patients.Methods: Immunohistochemistry was performed using a tumour tissue microarray of TNM (Tumour, Node, Metastasis)-stage I–IV CRC tissues. Single-marker expression or their combination was assessed for associations with the clinical outcome of CRC patients (N=309).Results: Increased expression of Aldh1 or Survivin, or decreased expression of EpCAM was each associated with poor clinical outcome, and was therefore identified as clinically unfavourable expression. Analyses of the combination of all three markers showed worse clinical outcome, specifically in colon cancer patients, with an increasing number of markers showing unfavourable expression. Hazard ratios ranged up to 8.3 for overall survival (P<0.001), 36.6 for disease-specific survival (P<0.001), and 27.1 for distant recurrence-free survival (P<0.001).Conclusions: Our data identified combined expression levels of Aldh1, Survivin, and EpCAM as strong independent prognostic factors, with high hazard ratios, for survival and tumour recurrence in colon cancer patients, and therefore reflect tumour aggressiveness. |
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Keywords: | colon neoplasms survival analysis recurrence ALDH1A1 protein BIRC5 protein EPCAM protein biomarkers cancer hallmarks |
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