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BACKGROUND: To deliver efficacious personalised cancer treatment, it is essential to characterise the cellular metabolism as well as the genetic stability of individual tumours. In this study, we describe a new axis between DNA repair and detoxification of aldehyde derivatives with important implications for patient prognosis and treatment. METHODS: Western blot and qPCR analyses were performed in relevant non-transformed and cancer cell lines from lung and liver tissue origin in combination with bioinformatics data mining of The Cancer Genome Atlas database from lung and hepatocellular cancer patients. RESULTS: Using both biochemical and bioinformatics approaches, we revealed an association between the levels of expression of the aldehyde detoxifying enzyme aldehyde dehydrogenase 2 (ALDH2) and the key DNA base excision repair protein XRCC1. Across cancer types, we found that if one of the corresponding genes exhibits a low expression level, the level of the other gene is increased. Surprisingly, we found that low ALDH2 expression levels associated with high XRCC1 expression levels are indicative for a poor overall survival, particularly in lung and liver cancer patients. In addition, we found that Mithramycin A, a XRCC1 expression inhibitor, efficiently kills cancer cells expressing low levels of ALDH2. CONCLUSIONS: Our data suggest that lung and liver cancers require efficient single-strand break repair for their growth in order to benefit from a low aldehyde detoxification metabolism. We also propose that the ratio of XRCC1 and ALDH2 levels may serve as a useful prognostic tool in these cancer types.

Original publication

DOI

10.1007/s13402-018-0390-8

Type

Journal article

Journal

Cell Oncol (Dordr)

Publication Date

10/2018

Volume

41

Pages

527 - 539

Keywords

ALDH2, Aldehydes, Base excision repair, DNA damage, Genetic instability, Liver and lung carcinomas, Mithramycin a, XRCC1, Aldehyde Dehydrogenase, Mitochondrial, Cell Line, Cell Line, Tumor, Cell Survival, DNA Damage, Humans, Liver Neoplasms, Lung Neoplasms, Plicamycin, RNA, Small Interfering, X-ray Repair Cross Complementing Protein 1