Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients
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 implicat...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Verlag
2018
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| _version_ | 1797071867330166784 |
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| author | Chen, X Legrand, A Cunniffe, S Hume, S Poletto, M Vaz, B Ramadan, K Yao, D Dianov, G |
| author_facet | Chen, X Legrand, A Cunniffe, S Hume, S Poletto, M Vaz, B Ramadan, K Yao, D Dianov, G |
| author_sort | Chen, X |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:59:27Z |
| format | Journal article |
| id | oxford-uuid:6193339b-4ad0-488f-9a59-4cdd4c58b9da |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:59:27Z |
| publishDate | 2018 |
| publisher | Springer Verlag |
| record_format | dspace |
| spelling | oxford-uuid:6193339b-4ad0-488f-9a59-4cdd4c58b9da2022-03-26T18:00:53ZInterplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patientsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6193339b-4ad0-488f-9a59-4cdd4c58b9daEnglishSymplectic Elements at OxfordSpringer Verlag2018Chen, XLegrand, ACunniffe, SHume, SPoletto, MVaz, BRamadan, KYao, DDianov, GBACKGROUND: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. |
| spellingShingle | Chen, X Legrand, A Cunniffe, S Hume, S Poletto, M Vaz, B Ramadan, K Yao, D Dianov, G Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients |
| title | Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients |
| title_full | Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients |
| title_fullStr | Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients |
| title_full_unstemmed | Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients |
| title_short | Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients |
| title_sort | interplay between base excision repair protein xrcc1 and aldh2 predicts overall survival in lung and liver cancer patients |
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