PMID- 23064051 OWN - NLM STAT- MEDLINE DCOM- 20130403 LR - 20220331 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 94 IP - 1 DP - 2013 Feb TI - Metallothionein 1F and 2A overexpression predicts poor outcome of non-small cell lung cancer patients. PG - 301-8 LID - S0014-4800(12)00153-0 [pii] LID - 10.1016/j.yexmp.2012.10.006 [doi] AB - Metallothioneins (MT) are intracellular, low molecular weight proteins (6-7 kDa) involved in binding of metal ions, scavenging of free radicals, cell proliferation and apoptosis and resistance to certain chemotherapeutics. Four basic families of MT proteins are distinguished: MT-I, MT-II, MT-III, MT-IV, within each of them different isoforms occur. The study aimed at examining the expression level of nine MT isoforms: MT-1A, -1B, -1E, -1F, -1G, -1H, -1X, MT-2A and MT-IV by using real-time PCR and MT-I/II expression by immunohistochemical (IHC) technique in 69 cases of non-small cell lung cancer (NSCLC) and 12 non-malignant lung tissues (NMLT) and to correlate them with patients clinicopathological data and Ki-67 antigen expression. Out of all the analyzed cases, 62 (89.9%) demonstrated an increased MT-I/II expression. MT-1B, 1F, -1G, -1H and MT-1X were significantly up-regulated, whereas MT-1E was significantly down-regulated in NSCLC as compared to NMLT. Only in two cases MT-IV mRNA expression was noted. Significant positive correlations were observed between each particular MT isoform expressions. Higher MT-1F and MT-1A mRNA expression was associated with larger primary tumor size (P=0.0362 and P<0.0001, respectively). Moreover, up-regulated MT-1F mRNA expression was associated with higher grade of malignancy of NSCLC (P=0.0085). Higher MT-1B mRNA expression was associated with squamocellular and adenocarcinoma subtype of NSCLC (P=0.0358). Univariate analysis showed, that up-regulated MT-1F and MT-2A mRNA predicted poor patients' survival (P=0.0206 and P=0.0097, respectively). The levels of MT-1F and MT-2A mRNA could be considered as new markers of poor prognosis of NSCLC patients. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Werynska, Bozena AU - Werynska B AD - Department of Pulmonology and Pulmonary Tumours, Medical University in Wroclaw, Poland. FAU - Pula, Bartosz AU - Pula B FAU - Muszczynska-Bernhard, Beata AU - Muszczynska-Bernhard B FAU - Gomulkiewicz, Agnieszka AU - Gomulkiewicz A FAU - Piotrowska, Aleksandra AU - Piotrowska A FAU - Prus, Robert AU - Prus R FAU - Podhorska-Okolow, Marzena AU - Podhorska-Okolow M FAU - Jankowska, Renata AU - Jankowska R FAU - Dziegiel, Piotr AU - Dziegiel P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121009 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Biomarkers, Tumor) RN - 0 (Ki-67 Antigen) RN - 0 (MT1F protein, human) RN - 0 (MT2A protein, human) RN - 0 (Protein Isoforms) RN - 0 (RNA, Messenger) RN - 9038-94-2 (Metallothionein) SB - IM MH - Biomarkers, Tumor/biosynthesis/genetics MH - Carcinoma, Non-Small-Cell Lung/*metabolism/pathology MH - Down-Regulation MH - Female MH - Humans MH - Ki-67 Antigen/biosynthesis MH - Lung Neoplasms/*metabolism/pathology MH - Male MH - Metallothionein/*biosynthesis/genetics MH - Middle Aged MH - Neoplasm Grading MH - Prognosis MH - Protein Isoforms/biosynthesis MH - RNA, Messenger/biosynthesis MH - Up-Regulation EDAT- 2012/10/16 06:00 MHDA- 2013/04/04 06:00 CRDT- 2012/10/16 06:00 PHST- 2012/05/13 00:00 [received] PHST- 2012/10/02 00:00 [revised] PHST- 2012/10/03 00:00 [accepted] PHST- 2012/10/16 06:00 [entrez] PHST- 2012/10/16 06:00 [pubmed] PHST- 2013/04/04 06:00 [medline] AID - S0014-4800(12)00153-0 [pii] AID - 10.1016/j.yexmp.2012.10.006 [doi] PST - ppublish SO - Exp Mol Pathol. 2013 Feb;94(1):301-8. doi: 10.1016/j.yexmp.2012.10.006. Epub 2012 Oct 9.