Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer.
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.
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
I J
IJ
Goossens-Beumer
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
E C M
EC
Zeestraten
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
A
A
Benard
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
T
T
Christen
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
M S
MS
Reimers
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
R
R
Keijzer
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
C F M
CF
Sier
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
G J
GJ
Liefers
Department of Pathology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
H
H
Morreau
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center Leiden 2300 RC, The Netherlands.
H
H
Putter
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
A L
AL
Vahrmeijer
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
C J H
CJ
van de Velde
Department of Surgery, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
P J K
PJ
Kuppen
D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000096:biosynthesis*; D000077022:Survivin; D046888:Tissue Array Analysis
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D000077022:Survivin; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase