The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis

Abstract

This meta-analysis aims to identify the diagnostic accuracy of mutations in the Kirsten Rat Sarcoma (KRAS) oncogene in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The survival of PDAC remains poor often due to the fact that disease is advanced at diagnosis. We analysed 22 studies, with a total of 2156 patients, to identify if the detection of KRAS mutations from pancreatic exocrine secretions yields sufficient specificity and sensitivity to detect patients with PDAC amongst healthy individuals. The majority of the studies were retrospective, samples were obtained endoscopically or surgically, and included comparator populations of patients with chronic pancreatitis and pre-malignant pancreatic lesions (PanIN) as well as healthy controls. We performed several analyses to identify the diagnostic accuracy for PDAC among these patient populations. Our results highlighted that the diagnostic accuracy of KRAS mutation for PDAC was of variable sensitivity and specificity when compared with PanINs and chronic pancreatitis, but had a higher specificity among healthy individuals. The sensitivity of this test must be improved to prevent missing early PDAC or PanINs. This could be achieved with rigorous prospective cohort studies, in which high-risk patients with normal cross-sectional imaging undergo surveillance following KRAS mutation testing.

Diagnostic value of neuronal pentraxin II methylation in patients with pancreatic cancer: Meta‐analysis

“…This could be used in detecting those patient population with unnormal cross‐sectional imaging. Recently, a diagnostic meta‐analysis of Mutant KRAS Detection in Pancreatic Secretions extracted 22 studies which demonstrated that testing of mutant KRAS can be applicable to a patient population at high risk of PDAC but with normal cross‐sectional imaging, which made up the rest part of our research in differentiating high‐risk healthy controls from PC 41 . Therefore, combining the detection of both biomarkers may help in separating PC from other situations, including benign diseases and healthy individuals.…”

“…It is obvious that promising specificity will help decrease unnecessary inspection or treatment which may result in infection or risk of metastasis. As previously reported, the mutant KRAS is of high specificity, however, its sensitivity is varied widely between studies as NPTX2 which may limited the application in the clinical practice 41 . Furthermore, combining with other investigation method would make it more suitable to be a screening test.…”

“…The reason for the dramatically varied sensitivity may be multifactorial, including the differences in the ethnicity, detected sites, the use of secretin stimulation, the ways to obtained the samples, and the detected approaches of the methylated NPTX2. It's also not correct to pool a diagnostic analysis when the samples were obtained by different method 41 . Therefore, the HROC curve was chosen to demonstrate the heterogeneity of different studies and further understand the intrinsic relationship between studies.…”

Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket?

“…Methylated DNA: Mutations in the KRAS oncogene are present in over 90% of resected PC specimens, with the vast majority of these mutations occurring in KRAS codon 12. A recent meta-analysis published by Patel et al [ 374 ], encompassing 22 studies aimed to assess the diagnostic accuracy of mutant KRAS detection from pancreatic secretions (mucus, secretions and juice) for the diagnosis of PC. They reported a wide variation in sensitivity (38%-89%) and specificity (13%-100%) for the diagnosis of PC through KRAS mutation testing in pancreatic secretions, with significant heterogeneity in diagnostic accuracy across the included studies.…”

“…They reported a wide variation in sensitivity (38%-89%) and specificity (13%-100%) for the diagnosis of PC through KRAS mutation testing in pancreatic secretions, with significant heterogeneity in diagnostic accuracy across the included studies. They also assessed whether KRAS mutation detection would be beneficial in diagnosing PC in a screening population, which similarly returned a sensitivity ranging from 21%-86%, however specificity improved remarkably to 82%-100%[ 374 ]. In addition to KRAS, Methylated ppENK and p16 were reported to be present in pancreatic juice in 90.9% and 18.2% respectively of patients diagnosed with PC, and due to normal pancreatic juice not containing methylated forms of this DNA, their presence was postulated to suggest the presence of PC[ 375 ].…”