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Br J Cancer. 2017 Nov 7;117(10):1537-1543. doi: 10.1038/bjc.2017.304. Epub 2017 Sep 7.

Aldehyde dehydrogenase 1B1: a novel immunohistological marker for colorectal cancer.

Author information

1
Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA.
2
Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
3
British Columbia Cancer Agency/Terry Fox Laboratory, Vancouver, BC V5Z 1L3, Canada.
4
Department of Pathology, Yale University, School of Medicine, New Haven, CT 06510, USA.
5
Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA.

Abstract

BACKGROUND:

Aldehyde dehydrogenase (ALDH) 1A1 is an immunohistological biomarker of various solid tumours, but has not been successfully proved as a colorectal cancer (CRC) marker. We recently reported that ALDH1B1, which has functional roles in tumourigenesis, may be a better CRC marker than ALDH1A1.

METHODS:

Human CRC explants and cell lines were analysed to identify candidate CRC markers from eight ALDH isozymes including ALDH1A1 and ALDH1B1. A tissue microarray, including paired specimens of normal and tumour tissues, was subsequently analysed to determine if candidate ALDHs could distinguish CRC from normal tissue.

RESULTS:

Based on mRNA analysis, ALDH1B1 and ALDH2 were selected as suitable candidates. These were strongly and regularly expressed in tumour tissue and cell lines, including highly tumourigenic cell populations (ALDH+CD44+ cells), while other ALDHs, including ALDH1A1, showed differential or low expression. No genetic alteration of ALDH1B1 in CRC was suggested by the relationships between mRNA and protein levels/enzymatic activities, and cDNA sequences of CRC cell lines. Tissue microarray findings showed that ALDH1B1, but not ALDH2, could distinguish CRC from normal tissue. Furthermore, ratios of ALDH1B1 to ALDH1A1 or ALDH2 were found to be powerful CRC indicators.

CONCLUSIONS:

These results suggest that ALDH1B1 is a novel human CRC biomarker.

PMID:
28881356
PMCID:
PMC5680456
DOI:
10.1038/bjc.2017.304
[Indexed for MEDLINE]
Free PMC Article

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