La scoperta potrebbe rivoluzionare i protocolli di screening di questa malattia che uccide fino al 95 % dei pazientii. La sopravvivenza dopo 5 anni dalla diagnosi del cancro al pancreas, riconosciuto quasi sempre troppo tardi, ha una probabilita’ del 5 %, perche’ il tumore non e’ individuato finche’ non ha gia’ creato metastasi. Nita Ahuja e il suo gruppo di ricercatori della John Hopkins University hanno scoperto che un test del sangue puo’ rilevare alterazioni epigenetiche predittrici della crescita del cancro nel pancreas, portando ad una diagnosi precoce di questa malattia. I ricercatori hanno usato il metodo Mob (Methylation on Beads) per identificare due piccole alterazioni nel sangue di malati di cancro al pancreas: nell’81 % dei 42 campioni esaminati, sono stati trovati due geni, il BNC1 e ADAMTS1, non presenti in persone senza cancro al pancreas o con una storia familiare di cancro al pancreas. Lo studio è pubblicato sulla rivista Clinical Cancer Research.
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HomNovel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer
1. Joo Mi Yi1,
2. Angela A. Guzzetta2,
3. Vasudev Bailey3,
4. Stephanie R. Downing4,
5. Leander Van Neste5,
6. Katherine B Chiappinelli6,
7. Brian Keeley3,
8. Alejandro Stark3,
9. Alexander Herrera7,
10. Christopher L Wolfgang8,
11. Emmanouil P. Pappou2,
12. Christine A. Iacobuzio-Donahue9,
13. Michael Goggins10,
14. James G. Herman11,
15. Tza-Huei Wang3,
16. Stephen B. Baylin12, and
17. Nita Ahuja13,*
+ Author Affiliations
1. 1Research Institute, DIRAMS
2. 2Dept. of Surgery, Johns Hopkins Medical Institutes
3. 3Biomedical Engineering, Johns Hopkins School of Medicine
4. 4Department of Surgery, Howard University College of Medicine
5. 5Bioinformatics, MdxHealth
6. 6Oncology, The Johns Hopkins University, School of Medicine
7. 7Surgery, Johns Hopkins School of Medicine
8. 8Surgery, Johns Hopkins University
9. 9Division of Gastrointestinal/Liver Pathology, The Johns Hopkins Hospital
10. 10Department of Pathology, Medicine and Oncology, The Johns Hopkins Medical Institutions
11. 11Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
12. 12Oncology, The Johns Hopkins University, SOM
13. 13Department of Medical Oncology, Johns Hopkins University School of Medicine
1. ↵* Corresponding Author:
Nita Ahuja, Department of Medical Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, CRB1 3rd floor, Baltimore, Maryland, 21287, United States nahuja1@jhmi.edu
Abstract
Purpose: Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer. Experimental Design: We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of 8 promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis including methylation and expression. We used a nanoparticle-enabled MOB (Methylation On Beads) technology to detect early stage pancreatic cancers by analyzing DNA methylation in patient serum. Results: We identified 2 novel genes, BNC1 (92%) and ADAMTS1, (68%) that showed a high frequency of methylation in pancreas cancers (n=143), up to 100% in PanIN-3 and 97% in Stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (n=42) from pancreas cancer patients, with a sensitivity for BNC1 of 79% (95%CI:66-91%) and for ADAMTS1 of 48% (95%CI:33-63%), while specificity was 89% for BNC1 (95%CI:76-100%) and 92% for ADAMTS1 (95%CI:82-100%). Overall sensitivity using both markers is 81% (95%CI:69-93%) and specificity is 85% (95%CI:71-99%). Conclusions: Promoter DNA methylation of BNC1 and ADAMTS1 are potential biomarkers to detect early stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early-detection of pancreatic cancer and has the potential to improve mortality from this disease.
Received October 15, 2012.
Revision received August 12, 2013.
Accepted September 15, 2013.
Copyright © 2013, American Association for Cancer Research. |
