Seven-Signal Proteomic Signature for Detection of Operable Pancreatic Ductal Adenocarcinoma and Their Discrimination from Autoimmune Pancreatitis

Kiyoshi Yanagisawa,Kazuo Tajima,Takashi Takahashi,Shuta Tomida,Hidemi Goto,Yoko Kuroyanagi,Chinatsu Arima,Nobumasa Mizuno,Masato Nagino,Toshiyuki Takeuchi,Shigeru B H Ko,Keitaro Matsuo,Takeo Kawahara,Kenji Yamao,Miyoko Kusumegi,Yukihiro Yokoyama

doi:10.1155/2012/510397

Abstract

There is urgent need for biomarkers that provide early detection of pancreatic ductal adenocarcinoma (PDAC) as well as discrimination of autoimmune pancreatitis, as current clinical approaches are not suitably accurate for precise diagnosis. We used mass spectrometry to analyze protein profiles of more than 300 plasma specimens obtained from PDAC, noncancerous pancreatic diseases including autoimmune pancreatitis patients and healthy subjects. We obtained 1063 proteomic signals from 160 plasma samples in the training cohort. A proteomic signature consisting of 7 mass spectrometry signals was used for construction of a proteomic model for detection of PDAC patients. Using the test cohort, we confirmed that this proteomic model had discrimination power equal to that observed with the training cohort. The overall sensitivity and specificity for detection of cancer patients were 82.6% and 90.9%, respectively. Notably, 62.5% of the stage I and II cases were detected by our proteomic model. We also found that 100% of autoimmune pancreatitis patients were correctly assigned as noncancerous individuals. In the present paper, we developed a proteomic model that was shown able to detect early-stage PDAC patients. In addition, our model appeared capable of discriminating patients with autoimmune pancreatitis from those with PDAC.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer death in Japan with more than 24,000 deaths annually [1], while 35,000 deaths each year in the United States are caused by the disease [2]
Agglomerative hierarchical clustering analysis using the identified proteomic signature showed a clear separation of plasma specimens from pancreatic ductal adenocarcinoma (PDAC) patients as compared to those from healthy individuals (Figure 1(b)), which confirmed that the selected MS signals were informative for discrimination of PDAC cases from healthy individuals
We analyzed the protein expression profiles of plasma specimens obtained from patients with PDAC, as well as acute and chronic pancreatitis cases, and autoimmune pancreatitis (AIP) patients with MALDI MS

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer death in Japan with more than 24,000 deaths annually [1], while 35,000 deaths each year in the United States are caused by the disease [2]. Long-term survival for PDAC patients remains unsatisfactory, with only 3–5% surviving for more than 5 years after surgical resection, with the remainder succumbing to widespread metastasis or massive local recurrence. The clinical symptoms of PDAC are often unremarkable until advanced stages of the disease, and the anatomic location of the pancreas deep in the abdomen makes physical detection and imaging approaches difficult. Serum markers for PDAC including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) play important roles in current clinical practice for monitoring progression and treatment response, as well as surveillance for recurrence, these markers are not ideal for cancer screening due to their low specificity and/or sensitivity in early stages of the disease [4,5,6]

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Conclusion