title: BCL2L12: a promising molecular prognostic biomarker in breast cancer.
abstract: OBJECTIVE
  BCL2-like 12 (BCL2L12) is a new member of the BCL2 gene family that was discovered and cloned by members of our group and found to be expressed in the mammary gland. Many genes of the BCL2 family were found to be implicated in breast carcinogenesis and to serve as possible prognostic markers. The aim of the present study was the quantification of BCL2L12 mRNA expression in order to assess its value as a prognostic tissue biomarker in breast cancer (BC).
  
  
  METHODS
  BCL2L12 mRNA levels were determined in a statistically significant sample size of cancerous (N=108) and adjacent non-cancerous (N=71) breast tissues using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Relative quantification analysis was conducted using the comparative C(T) (2(-ΔΔC)(T)) method, whereas the association between BCL2L12 expression and clinopathological data, disease-free survival (DFS) and overall survival (OS) were estimated by statistical analysis.
  
  
  RESULTS
  BCL2L12 mRNA expression was decreased in malignant samples compared to the histologically normal counterparts (p=0.012). Significant relationships between BCL2L12 expression and TNM stages (p=0.009), metastatic potential (p=0.012), tumor size (p=0.04) and age (p=0.024) were observed. Moreover, Kaplan-Meier and Cox univariate analyses indicated that BCL2L12 expression is associated with longer DFS, whereas multivariate analysis pointed out the independent favorable prognostic value of BCL2L12.
  
  
  CONCLUSIONS
  According to our results, BCL2L12 mRNA expression is a favorable prognostic marker of DFS for BC patients, suggesting its possible application as a novel prognostic indicator of this malignancy.
authors.affiliation: First Department of Medical Oncology, "Saint Savvas", Anticancer Hospital, 11522, Athens, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tzovaras
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, 15701 Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Kladi-Skandali
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, 15701 Athens, Greece.
authors.forename: Kleita
authors.initials: K
authors.lastname: Michaelidou
authors.affiliation: First Propaedeutic Surgical Department, Athens Medical School, "Hippokration" General Hospital, Athens, Greece.
authors.forename: George C
authors.initials: GC
authors.lastname: Zografos
authors.affiliation: The Breast Clinic "Saint Savvas", Anticancer Hospital, 11522,Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Missitzis
authors.affiliation: First Department of Medical Oncology, "Saint Savvas", Anticancer Hospital, 11522, Athens, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ardavanis
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, 15701 Athens, Greece. Electronic address: ascorilas@biol.uoa.gr.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C430100:BCL2L12 protein, human; D014408:Biomarkers, Tumor; D009124:Muscle Proteins; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Apoptosis; BCL2 family; Molecular tumor markers; Prognostic biomarker; Quantitative real-time PCR