Pancreatic cancer is technically a deadly late bloomer. It becomes clinically visible only at an advanced stage, making management and recovery extremely difficult.
However, researchers from the United Kingdom have found the presence of three proteins in urine to be effective early biomarkers for pancreatic cancer. They have also devised a simple non-invasive urine test to detect the level of these proteins to predict the risk of pancreatic cancer at least two years before clinical diagnosis.
“This is very important because if pancreatic ductal adenocarcinoma (PDAC) is detected earlier, when it is small and still localised to the pancreas, the person’s survival chances can increase to over 60%,” Prof Dr Tatjana Crnogorac-Jurcevic, professor of molecular pathology and biomarkers and group leader, pancreatic biomarkers group, Barts Cancer Research Institute, Queen Mary University, London, told Happiest Health in an online interaction.
What is pancreatic ductal adenocarcinoma?
According to the American Cancer Society, pancreatic cancer doesn’t have any symptoms during its onset and it later camouflages behind an array of pancreatic and liver complications including jaundice, liver enlargement and even diabetes.
Prof Dr Crnogorac-Jurcevic points out that PDAC is the most common pancreatic cancer and is the outcome of cancerous growth in the exocrine glands of the pancreas responsible for secreting digestive enzymes. It usually starts in the pancreatic ducts.
“When symptoms appear, they are usually non-specific and often intermittent, so over 80% of patients are diagnosed at an advanced stage, when the tumour is either locally advanced or has already spread to other organs,” she adds.
Prof Dr Crnogorac-Jurevic says that often less than 10% of people diagnosed with advanced pancreatic cancer live for more than five years.
Urinary biomarkers of pancreatic cancer
Prof Dr Crnogorac-Jurcevic and her team made the first breakthrough by confirming elevated levels of three proteins in urine samples of people diagnosed with pancreatic cancer. Samples collected from healthy donors and those with pancreatitis did not have this variation.
“These three proteins are TFF1, REG1B and LYVE1,” she says. “The level of expression of all of these three biomarkers is increased in PDAC.”
She adds that TFF1 is a small 9 kDa protein involved in protection of gastrointestinal tract mucosa. “It is not present in normal pancreas but is expressed in precursor lesions from which pancreatic cancer develops and in more than 70% of people with PDAC,” she says.
She also adds that REG1B is a 19 kDa protein, involved in regeneration of damaged tissues, and it is also — similarly to TFF1 — expressed in precursor lesions and the majority of pancreatic cancers. While it is expressed in normal pancreas, it is only secreted in precancerous and cancerous pancreatic tissue, and can thus be detected in urine. LYVE1 is the third protein found elevated in people with pancreatic cancer.
“LYVE1 is 35 kDa protein whose biological role at the moment is not well-established and we do not know what it does in PDAC,” Prof Dr Crnogorac-Jurcevic adds.
The PancRISK score and UroPanc trial
The research team also came up with a risk assessment score called PancRISK (like the Framingham risk score for heart health) to screen and assess the risk of PDAC and decide who should be made to undergo further tests to decide their cancer treatment course.
“PancRISK is an algorithm to interpret the obtained data on three biomarkers which also includes patients’ age,” she says. “It calculates the risk of developing PDAC (it is either ‘elevated’ or ‘normal’), so it is a stratification tool for flagging patients who need to undergo further, usually invasive and expensive clinical workup.”
She explains that PancRISK provides a step towards precision surveillance for PDAC patients, which is now being done in a clinical trial, UroPanc. The trial is being carried out by researchers from the Barts Cancer Institute and funded by the Pancreatic Cancer Research Fund, UK’s national charity.
“A standardised test for measuring the three proteins in urine has been developed and will be used to assay the urine samples collected from over 2,000 patients, including the asymptomatic individuals who have increased chance of developing PDAC due to genetics, as well as symptomatic patients attending gastroenterology clinics due to vague symptoms that are suggestive of PDAC,” she says.
Asked about the accuracy of the protein biomarker-based urinary test, Prof Dr Crnogorac-Jurcevic says, “Both the sensitivity and specificity of the PDAC detection are greater than 80%.”
‘Late detection of pancreatic cancer a major concern’
Dr Neeraj Dhamija, gastrointestinal surgeon, Sir Ganga Ram Hospital, New Delhi, who is not directly involved in this research, points out that apart from late detection, the location of pancreas — nestled alongside the liver, gall bladder, spleen and duodenum (small intestine) — enhances the health risk.
“There are very high chances of the cancer already spreading to these nearby organs at the time of detection,” Dr Dhamija adds.
He says that screening of the pancreas through an ultrasound scan should be made compulsory for those diagnosed with severe jaundice, hepatitis and gastro complications such as dyspepsia lasting for more than six weeks. Dr Dhamija says smoking, obesity and chronic pancreatitis are among the major risk factors for pancreatic cancer.
Pancreatic cancer is always detected at an advanced stage, but the level of three proteins in urine samples could predict its risk in advance. Experts identify smoking, obesity and chronic pancreatitis as the major risk factors.