CD24 and APC Genetic Polymorphisms in Pancreatic Cancers as Potential Biomarkers for Clinical Outcome

• Published in: PloS one 2015-09, Vol.10 (9), p.e0134469-e0134469
• Main Authors: Shamai, Sivan, Nabiochtchikov, Ilana, Kraus, Sarah, Zigdon, Sally, Kazanov, Dina, Itzhak-Klutch, Michal, Eizner, Carmit, Arber, Nadir, Geva, Ravit
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenomatous polyposis coli; Adenomatous polyposis coli protein; Adenomatous Polyposis Coli Protein - genetics; Adult; Aged; Aged, 80 and over; Alleles; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Cancer; Cancer metastasis; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; CD24 Antigen - genetics; Chemotherapy; Clinical outcomes; Colorectal cancer; Deoxyribonucleic acid; Development and progression; Diagnosis; Disease prevention; DNA; DNA, Neoplasm - analysis; Esophagus; Female; Genes; Genetic aspects; Genetic disorders; Genetic diversity; Genetic research; Genetic transformation; Genetic variance; Genotype; Heterozygote; Heterozygotes; Homozygote; Humans; Kaplan-Meier Estimate; Male; Malignancy; Medical diagnosis; Medical prognosis; Medical research; Metastases; Middle Aged; Mortality; Mutation; Neoplasm Metastasis; Oncology; Ovarian cancer; Pancreatic cancer; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Patient outcomes; Patients; Polymorphism, Single Nucleotide; Polyposis coli; Polyps; Prognosis; Prostate cancer; Proteins; Real-Time Polymerase Chain Reaction; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Survival; Transformation; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0134469

There are no validated biomarkers that correlate with the prognosis of pancreatic ductal adenocarcinoma (PDA). The CD24 and adenomatous polyposis coli (APC) genes are important in the malignant transformation of gastrointestinal cells. This study examined APC and CD24 genetic polymorphisms and their possible impact on survival of patients with PDA. Clinical and pathological data as well as blood samples for extracting DNA were obtained for 73 patients with PDA. Real-time PCR assessed genetic variants of APC (I1307K and E1317Q), and four different single nucleotide polymorphisms (SNPs) in the CD24 gene: C170T (rs52812045), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818). The median age at diagnosis was 64 (41-90) years. Thirty-one patients (42.5%) were operable, 16 (22%) had locally advanced disease and 26 (35.5%) had disseminated metastatic cancer. The malignancy-related mortality rate was 84%. Median survival was 14 months (11.25-16.74). Survival was similar for wild-type (WT), heterozygous and homozygous variants of the APC or CD24 genes. The three most frequent CD24 SNP combinations were: heterozygote for A1626G and WT for the rest of the alleles (14% of patients), heterozygote for C170T, A1626G, A1056G and WT for the rest (14% of patients), and heterozygote for C170T, A1056G and WT for the rest (10% of patients). All patients were APC WT. The first two groups were significantly younger at diagnosis than the third group. Specific polymorphisms in the APC and CD24 genes may play a role in pancreatic cancer development. Correlation with survival requires a larger cohort.