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

<div><p>Background</p><p>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).</p><p>Material and Methods</p><p>ME and ACLY expression was analyzed in 258 NSCLC in correlation with clinico-pathological parameters including patient’s survival.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div

Immunohistological expression of ACLY (A – D) and ME (E – H).

<p>(A)–(D) Specific ACLY-expression was detectable in the nucleus, or in the cytoplasm. (A); tumor tissue without specific ACLY staining—intensity score = 0; (B) weak specific cytoplasmic ACLY staining—intensity score = 1; (C) moderate nuclear ACLY staining—intensity score = 2 and moderate cytoplasmic ACLY staining—intensity score = 2; (D) strong cytoplasmic ACLY staining—intensity score = 3, additionally moderate nuclear staining is present; (E)–(H) Specific cytoplasmic expression of ME, (E) tumor tissue without specific cytoplasmic ME staining—intensity score = 0 (F); weak specific cytoplasmic ME staining—intensity score = 1 (G); moderate cytoplasmic ME staining—intensity score = 2 (H) and with strong specific cytoplasmic ME staining—intensity score = 3 (E). (Magnification; 20x)</p