Quantitative expression analysis and prognostic significance of the novel apoptosis-related gene BCL2L12 in colon cancer.
Apoptosis is a tightly regulated process that plays a critical role in many biological events. Members of the BCL2 (Bcl-2) family of apoptosis-related genes have been found to be differentially expressed in various malignancies and have been proposed as prognostic tumor biomarkers. We have recently discovered and cloned a new member of the BCL2 gene family, BCL2L12, expressed in colon tissues. Here we have investigated expression of the BCL2L12 gene in colon cancer tissues and assessed its prognostic value. Total RNA was isolated from 96 specimens of malignant colon tissue. After testing the RNA quality, cDNA was prepared by reverse transcription. A highly sensitive real-time PCR method for BCL2L12 mRNA quantification was developed using SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative C(T) method (2(-DeltaDeltaCT)). High BCL2L12 expression levels were found in smaller (< or =5 cm, p=0.027) and well-differentiated tumors (p=0.034), as well as in early-stage tumors (p=0.039). Survival analysis demonstrated that patients with BCL2L12-positive colon tumors have significantly longer disease-free survival and overall survival (p=0.015 and p=0.027, respectively). Our results suggest that BCL2L12 gene expression may represent a potential new biomarker for colon cancer.
Kontos
Christos K
CK
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, GR-15701 Athens, Greece.
Papadopoulos
Iordanis N
IN
Scorilas
Andreas
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D052160:Benzothiazoles; D014408:Biomarkers, Tumor / Q000235:genetics; D003106:Colon / Q000737:chemistry / Q000473:pathology; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003959:Diamines; D005260:Female; D005456:Fluorescent Dyes; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009930:Organic Chemicals; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D011804:Quinolines; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
C430100:BCL2L12 protein, human; D052160:Benzothiazoles; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D003959:Diamines; D005456:Fluorescent Dyes; D009124:Muscle Proteins; D009930:Organic Chemicals; D019253:Proto-Oncogene Proteins c-bcl-2; D011804:Quinolines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C098022:SYBR Green I