title: Prognostic impact of Bcl-2 depends on tumor histology and expression of MALAT-1 lncRNA in non-small-cell lung cancer.
abstract: BACKGROUND
  Apoptosis is a crucial pathway in tumor growth and metastatic development. Apoptotic proteins regulate the underlying molecular cascades and are thought to modulate the tumor response to chemotherapy and radiation. However, the prognostic value of the expression of apoptosis regulators in localized non-small-cell lung cancer (NSCLC) is still unclear.
  
  
  METHODS
  We investigated the protein expression of apoptosis regulators Bcl-2, Bcl-xl, Mcl-1, and pp32/PHAPI, and the expression of the lncRNA MALAT-1 in tumor samples from 383 NSCLC patients (median age: 65.6 years; 77.5% male; paraffin-embedded tissue microarrays). For statistical analysis correlation tests, Log rank tests and Cox proportional hazard models were applied.
  
  
  RESULTS
  Tumor histology was significantly associated with the expression of Bcl-2, Bcl-xl and Mcl-1 (all p < 0.001). Among the tested apoptotic markers only Bcl-2 demonstrated prognostic impact (hazard ratio = 0.64, p = 0.012). For NSCLC patients with non-adenocarcinoma histology, Bcl-2 expression was associated with increased overall survival (p = 0.036). Besides tumor histology, prognostic impact of Bcl-2 was also found to depend on MALAT-1 lncRNA expression. Gene expression analysis of A549 adenocarcinoma cells with differential MALAT-1 lncRNA expression demonstrated an influence on the expression of Bcl-2 and its interacting proteins.
  
  
  CONCLUSIONS
  Bcl-2 expression was specifically associated with superior prognosis in localized NSCLC. An interaction of Bcl-2 with MALAT-1 lncRNA expression was revealed, which merits further investigation for risk prediction in resectable NSCLC patients.
authors.affiliation: *Department of Medicine A, Hematology, Oncology and Pulmonology, University Hospital Muenster; †Institute of Biostatistics and Clinical Research, Westfaelische Wilhelms-Universitaet Muenster; ‡Gerhard-Domagk Institute of Pathology, University Hospital Muenster, Muenster; §Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen; ‖German Cancer Consortium (DKTK), Heidelberg; ¶Integrated Functional Genomics, Interdisciplinary Center for Clinical Research, University of Muenster, Muenster; #Chest Surgery, Klinikum St. Georg, Ostercappeln, Ostercappeln, Germany; and **Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Lars Henning
authors.initials: LH
authors.lastname: Schmidt
authors.forename: Dennis
authors.initials: D
authors.lastname: Görlich
authors.forename: Tilmann
authors.initials: T
authors.lastname: Spieker
authors.forename: Christian
authors.initials: C
authors.lastname: Rohde
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.forename: Michael
authors.initials: M
authors.lastname: Mohr
authors.forename: Julia
authors.initials: J
authors.lastname: Humberg
authors.forename: Tim
authors.initials: T
authors.lastname: Sauer
authors.forename: Nils H
authors.initials: NH
authors.lastname: Thoenissen
authors.forename: Andreas
authors.initials: A
authors.lastname: Huge
authors.forename: Reinhard
authors.initials: R
authors.lastname: Voss
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marra
authors.forename: Andreas
authors.initials: A
authors.lastname: Faldum
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Rainer
authors.initials: R
authors.lastname: Wiewrodt
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C557041:MALAT1 long non-coding RNA, human; D019253:Proto-Oncogene Proteins c-bcl-2; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm