Tags

Type your tag names separated by a space and hit enter

Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.

Abstract

BACKGROUND & AIMS

Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls).

METHODS

We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees.

RESULTS

We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%).

CONCLUSIONS

We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: majumder.shounak@mayo.edu.Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.Exact Sciences Corporation, Madison, Wisconsin.Exact Sciences Corporation, Madison, Wisconsin.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31323382

Citation

Majumder, Shounak, et al. "Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 2019.
Majumder S, Raimondo M, Taylor WR, et al. Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls. Clin Gastroenterol Hepatol. 2019.
Majumder, S., Raimondo, M., Taylor, W. R., Yab, T. C., Berger, C. K., Dukek, B. A., ... Ahlquist, D. A. (2019). Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, doi:10.1016/j.cgh.2019.07.017.
Majumder S, et al. Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls. Clin Gastroenterol Hepatol. 2019 Jul 16; PubMed PMID: 31323382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls. AU - Majumder,Shounak, AU - Raimondo,Massimo, AU - Taylor,William R, AU - Yab,Tracy C, AU - Berger,Calise K, AU - Dukek,Brian A, AU - Cao,Xiaoming, AU - Foote,Patrick H, AU - Wu,Chung Wah, AU - Devens,Mary E, AU - Mahoney,Douglas W, AU - Smyrk,Thomas C, AU - Pannala,Rahul, AU - Chari,Suresh T, AU - Vege,Santhi Swaroop, AU - Topazian,Mark D, AU - Petersen,Bret T, AU - Levy,Michael J, AU - Rajan,Elizabeth, AU - Gleeson,Ferga C, AU - Dayyeh,Barham Abu, AU - Nguyen,Cuong C, AU - Faigel,Douglas O, AU - Woodward,Timothy A, AU - Wallace,Michael B, AU - Petersen,Gloria, AU - Allawi,Hatim T, AU - Lidgard,Graham P, AU - Kisiel,John B, AU - Ahlquist,David A, Y1 - 2019/07/16/ PY - 2018/12/18/received PY - 2019/07/10/revised PY - 2019/07/12/accepted PY - 2019/7/20/pubmed PY - 2019/7/20/medline PY - 2019/7/20/entrez KW - Chemistry KW - Neoplasm KW - Prognostic KW - Secretin JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin. Gastroenterol. Hepatol. N2 - BACKGROUND & AIMS: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls). METHODS: We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees. RESULTS: We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%). CONCLUSIONS: We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/31323382/Methylated_DNA_in_Pancreatic_Juice_Distinguishes_Patients_With_Pancreatic_Cancer_From_Controls L2 - https://linkinghub.elsevier.com/retrieve/pii/S1542-3565(19)30750-5 DB - PRIME DP - Unbound Medicine ER -