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

• Published in: PloS one 2015-05, Vol.10 (5), p.e0126357-e0126357
• Main Authors: Csanadi, Agnes, Kayser, Claudia, Donauer, Marcel, Gumpp, Vera, Aumann, Konrad, Rawluk, Justyna, Prasse, Antje, zur Hausen, Axel, Wiesemann, Sebastian, Werner, Martin, Kayser, Gian
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Aged; ATP; ATP Citrate (pro-S)-Lyase - metabolism; ATP citrate lyase; Biology; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - pathology; Cell metabolism; Cellular manufacture; Correlation analysis; Dehydrogenases; Enzyme regulation; Enzymes; Ethics; Fatty acids; Genetic aspects; Geriatrics; Glucose; Glycolysis; Health aspects; Humans; Immunohistochemistry; Kinases; Lung cancer; Lung diseases; Lymph nodes; Malate Dehydrogenase - metabolism; Malic enzyme; Medical prognosis; Metabolic pathways; Metabolism; Metabolites; Metastases; Middle Aged; Mutation; Non-small cell lung cancer; Non-small cell lung carcinoma; Nucleotides; Older people; Oncology; Pathology; Patients; Prognosis; Survival; Thoracic surgery; Tissues; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126357

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). ME and ACLY expression was analyzed in 258 NSCLC in correlation with clinico-pathological parameters including patient's survival. 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. 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.