Biomarkers for distinguishing benign, pre-malignant, and malignant pancreatic cysts
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsWalter G. Park, Pankaj J. Pasricha, Gary Peltz, Anson Lowe
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Abstract
Methods for prognosis and diagnosis of pancreatic cysts are disclosed. In particular, the invention relates to the use of biomarkers from pancreatic cyst fluid to aid in the diagnosis, prognosis, and treatment of pancreatic cysts. More specifically, differential expression of certain metabolites, including glucose and kynurenine, and the protein, amphiregulin, is used to distinguish benign, pre-malignant, and malignant pancreatic cysts.
Claims39
A method for distinguishing mucinous and non-mucinous cysts, the method comprising:
- a) obtaining a sample of pancreatic cyst fluid from a subject;
- b) measuring the levels of one or more biomarkers in the pancreatic cyst fluid, wherein the one or more biomarkers are selected from the group consisting of glucose and kynurenine;
- and
- c) analyzing the levels of one or more biomarkers in conjunction with respective reference levels for the biomarkers, wherein similarity of the levels of one or more biomarkers in the cyst fluid to reference value levels for a mucinous cyst indicates that the cyst in the subject is a mucinous cyst, and wherein similarity of the levels of one or more biomarkers in the cyst fluid to reference levels for a non-mucinous cyst indicates that the cyst in the subject is a non-mucinous cyst.
A method for determining the malignant potential of a pancreatic cyst in a subject, the method comprising:
- a) obtaining a sample of pancreatic cyst fluid from a subject,
- b) measuring the amount of amphiregulin in the pancreatic cyst fluid derived from the subject, and
- c) analyzing the amount of amphiregulin in conjunction with reference levels for amphiregulin, wherein the reference levels are determined by analyzing the amounts of amphiregulin in pancreatic cyst fluid samples derived from subjects with malignant mucinous pancreatic cysts, wherein the amount of amphiregulin in the pancreatic cyst fluid sample is correlated with the malignant potential of the pancreatic cyst.
A method of monitoring a pancreatic cyst in a subject, the method comprising:
- a) analyzing a first pancreatic cyst fluid sample from a subject to determine the levels of one or more biomarkers, wherein the one or more biomarkers are selected from the group consisting of glucose, kynurenine, and amphiregulin, wherein the first sample is obtained from the subject at a first time point;
- b) analyzing a second pancreatic cyst fluid sample from the subject to determine the levels of the one or more biomarkers, wherein the second sample is obtained from the subject at a second time point;
- and
- c) comparing the levels of the one or more biomarkers in the first pancreatic cyst fluid sample to the levels of the one or more biomarkers in the second pancreatic cyst fluid sample in order to detect any changes in the status of the pancreatic cyst in the subject over time.
A method for treating a pancreatic cyst in a subject, the method comprising:
- obtaining a sample of pancreatic cyst fluid from the pancreatic cyst in the subject, and surgically removing the pancreatic cyst from the subject if the level of amphiregulin in the pancreatic cyst fluid sample is greater than 300 pg/ml.
A method for determining the prognosis of a subject who has a pancreatic cyst, the method comprising:
- a) obtaining a sample of pancreatic cyst fluid from the subject,
- b) measuring the amount of glucose in the pancreatic cyst fluid derived from the subject, wherein a level of glucose greater than or equal to 66 mg/dL indicates that the subject is at low risk of developing pancreatic cancer;
- and
- c) measuring the amount of amphiregulin in the pancreatic cyst fluid derived from the subject, wherein a level of amphiregulin greater than 300 pg/ml indicates that the subject is at high risk of developing pancreatic cancer.
A method for monitoring the efficacy of a therapy for treating pancreatic cancer or dysplasia in a subject, the method comprising:
- analyzing the levels of amphiregulin in pancreatic cyst fluid samples derived from the subject before and after the subject undergoes said therapy, in conjunction with respective reference levels for amphiregulin.
A biomarker panel for diagnosing pancreatic cysts comprising one or more biomarkers selected from the group consisting of glucose, kynurenine, and amphiregulin.
A kit comprising agents for measuring the levels of one or more biomarkers in pancreatic cyst fluid from a subject, wherein the one or more biomarkers are selected from the group consisting of glucose, kynurenine, and amphiregulin;
- and instructions for using the kit to diagnose pancreatic cysts.
Dependencies are inferred from the claim text.