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

Additional file 3: Table S2. of Tumour stage distribution and survival of malignant melanoma in Germany 2002–2011

Malignant melanoma patients aged 35 years and above by age at diagnosis, sex, UICC stage, year of diagnosis, place of residence and ‘diagnosis during screening’, N = 34 739 (UICC 0 and X excluded) (DOCX 40 kb

Additional file 4: Table S3. of Tumour stage distribution and survival of malignant melanoma in Germany 2002–2011

Relative 5-year survival of malignant melanoma patients diagnosed between 2002 and 2011, overall (UICC 0-IV, X) (N = 60 672) and for patients with invasive tumours (UICC I – IV, X) stratified by age, sex, UICC stage, ‘diagnosis during screening’ and place of residence (N = 49 351) (DOCX 39 kb