Researchers have identified diagnostic microRNA panels in whole blood that had the ability to distinguish, to some degree, patients with and without pancreatic cancer, according to a study in the January 22/29 issue of JAMA. The authors caution that the findings are preliminary, and that further research is necessary to understand whether these microRNAs have clinical implications as a screening test for early detection of pancreatic cancer.
MicroRNAs regulate gene expression and play important roles in the development of tumors and tumor metastasis. MicroRNA panels are a combination of several microRNAs.
Pancreatic cancer is the fourth most common cause of cancer death in the Western world and prognosis is poor, according to background information in the article. Early diagnosis of pancreatic cancer is difficult partly because it is difficult to get useful biopsies of tissue from patients suspected of having pancreatic cancer, so markers of the disease that could help with early diagnosis are needed to improve prognosis. Several specific microRNA profiles (patterns of microRNAs) have been linked to pancreatic cancer tissue. A diagnostic noninvasive blood test for pancreatic cancer would be very valuable, the authors write.
Nicolai A. Schultz, M.D., Ph.D., of Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues examined differences in microRNA in whole blood between patients with pancreatic cancer (n = 409) and healthy participants (n = 312) and patients with chronic pancreatitis (n = 25) to identify diagnostic panels of microRNAs for use in the diagnosis of pancreatic cancer. Serum cancer antigen 19-9 (CA19-9; an antigen that is elevated in approximately 80 percent of patients with pancreatic cancer) was also measured for comparison.
The researchers identified 2 novel panels with the potential for diagnosing pancreatic cancer.
The authors write that the test could result in referral of more individuals with symptoms to imaging. “The test could thereby diagnose more patients with pancreatic cancer, some of them at an early stage, and thus have a potential to increase the number of patients that can be operated on and possibly cured of pancreatic cancer.”
Pancreatic Cancer Diagnosis and Early Detection
Pancreatic cancer may go undetected until it’s advanced. By the time symptoms occur, diagnosing pancreatic cancer is usually relatively straightforward. Unfortunately, a cure is rarely possible at that point.
Diagnosing pancreatic cancer usually happens when someone comes to the doctor after experiencing weeks or months of symptoms. Pancreatic cancer symptoms frequently include abdominal pain, weight loss, itching, or jaundice (yellow skin). A doctor then embarks on a search for the cause, using the tools of the trade:
By taking a medical history, a doctor learns the story of the illness, such as the time of onset, nature and location of pain, smoking history, and other medical problems.
During a physical exam, a doctor might feel a mass in the abdomen and notice swollen lymph nodes in the neck, jaundiced skin, or weight loss.
Lab tests may show evidence that bile flow is being blocked, or other abnormalities.
Based on a person’s exam, lab tests, and description of symptoms, a doctor often orders an imaging test:
- Computed tomography (CT scan): A scanner takes multiple X-ray pictures, and a computer reconstructs them into detailed images of the inside of the abdomen. A CT scan helps doctors make a pancreatic cancer diagnosis.
- Magnetic resonance imaging (MRI): Using magnetic waves, a scanner creates detailed images of the abdomen, in particular the area around the pancreas, liver, and gallbladder.
- Ultrasound: Harmless sound waves reflected off organs in the belly create images, potentially helping doctors make a pancreatic cancer diagnosis.
- Positron emission tomography (PET scan): Radioactive glucose injected into the veins is absorbed by cancer cells. PET scans may help determine the degree of pancreatic cancer spread.
They add that the harms of a high number of false-positives in screening for pancreatic cancer using an inexpensive, noninvasive blood sample from individuals with or without symptoms should be quantified in the future.
“Although we validated the panels, our findings are preliminary. … Further research is necessary to understand whether these have clinical implications for early detection of pancreatic cancer and how much this information adds to serum CA19-9.”
(doi:10.1001/jama.2013.284664; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Early Detection of Pancreatic Cancer
There is currently no standard diagnostic tool or established early detection method for pancreatic cancer. When diagnosed early, surgical resection offers the best chance for long term control of pancreatic cancer, yet most patients are diagnosed at later stages and are not eligible for surgery. Therefore, tests sensitive enough to detect pancreatic cancer in the earliest stages are urgently needed.
Pancreatic cancer is diagnosed primarily through the use of computed tomography (CT) scans, magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP), laparoscopy and biopsy. Unfortunately, these tests have not proven to be 100% effective at detecting small lesions, pre-cancers or early stage cancers, which may be more possible to effectively treat.
For individuals who are at increased risk due to family history or other factors, effective early screening methods are especially important. A blood test that identifies a specific substance in the blood that is highly indicative of cancer, such as the PSA test for prostate cancer, is the ideal early detection method because of ease of use and cost-effectiveness. At institutions across the country, researchers are actively looking for pancreatic cancer biomarkers that can be used in a diagnostic test. Researchers use a variety of methods to find these markers and they are beginning to yield promising results.
Until a reliable early detection test is developed, screening protocols for high-risk individuals are very important. Although many doctors agree that having two or more close family members with pancreatic cancer puts a person at high risk for the disease, there is no consensus as to when, how often and with what methods these individuals should be screened.
Because of the lack of knowledge surrounding early screenings, doctors stress the importance of taking part in investigational studies targeted specifically at populations at high risk for pancreatic cancer. Two types of research programs for high-risk individuals are surveillance programs and family registries.
Editorial: Will Detection of MicroRNA Biomarkers in Blood Improve the Diagnosis and Survival of Patients With Pancreatic Cancer?
In an accompanying editorial, Donald J. Buchsbaum, Ph.D., of the University of Alabama, Birmingham, and Carlo M. Croce, M.D., of Ohio State University, Columbus, write that additional research is needed regarding the use of microRNAs for the early detection of pancreatic cancer.
“Even though the study was relatively large, well-conducted, and addressed the important topic of development of noninvasive methods to detect pancreatic cancer, the authors appropriately acknowledge the exploratory nature of the investigation. … Given the dismal prognosis for patients with pancreatic cancer, it is important that new diagnostic approaches, such as the one used in this study, are sought. However, additional rigorous investigation will be necessary to support and extend these interesting findings.”
Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
Julia S. Johansen
The JAMA Network Journals