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Prognostic Value of Malic Enzyme and ATP-Citrate Lyase in Non-Small Cell Lung Cancer of the Young and the Elderly.

AbstractBACKGROUND:
Lung cancer is the leading cause of death among malignancies worldwide. Understanding its biology is therefore of pivotal importance to improve patient's prognosis. In contrast to non-neoplastic tissues, cancer cells utilize glucose mainly for production of basic cellular modules '(i.e. nucleotides, aminoacids, fatty acids). In cancer, Malic enzyme (ME) and ATP-citrate lyase (ACLY) are key enzymes linking aerobic glycolysis and fatty acid synthesis and may therefore be of biological and prognostic significance in non-small cell lung cancer (NSCLC).
MATERIAL AND METHODS:
ME and ACLY expression was analyzed in 258 NSCLC in correlation with clinico-pathological parameters including patient's survival.
RESULTS:
Though, overall expression of both enzymes correlated positively, ACLY was associated with local tumor stage, whereas ME correlated with occurrence of mediastinal lymph node metastases. Young patients overexpressing ACLY and/or ME had a significantly longer overall survival. This proved to be an independent prognostic factor. This contrasts older NSCLC patients, in whom overexpression of ACLY and/or ME appears to predict the opposite.
CONCLUSION:
In NSCLC, ME and ACLY show different enzyme expressions relating to local and mediastinal spread. Most important, we detected an inverse prognostic impact of ACLY and/or ME overexpression in young and elderly patients. It can therefore be expected, that treatment of NSCLC especially, if targeting metabolic pathways, requires different strategies in different age groups.
AuthorsAgnes Csanadi, Claudia Kayser, Marcel Donauer, Vera Gumpp, Konrad Aumann, Justyna Rawluk, Antje Prasse, Axel zur Hausen, Sebastian Wiesemann, Martin Werner, Gian Kayser
JournalPloS one (PLoS One) Vol. 10 Issue 5 Pg. e0126357 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID25962060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Malate Dehydrogenase
  • ATP Citrate (pro-S)-Lyase
Topics
  • ATP Citrate (pro-S)-Lyase (metabolism)
  • Aged
  • Carcinoma, Non-Small-Cell Lung (enzymology, pathology)
  • Humans
  • Immunohistochemistry
  • Malate Dehydrogenase (metabolism)
  • Middle Aged
  • Prognosis

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