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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis
PDAC develops through the step-wise accumulation of mutations in tumour suppressor and oncogenes [12] accompanied by histological progression from benign precursor lesions (PanIN) to invasive malignancy and metastases [13,14]
The studies were generally of a moderate risk of bias (Table 1), with poor use of follow-up to assess whether patients with a control group who are Kirsten Rat Sarcoma (KRAS) positive develop PDAC
Summary
Despite the enhanced understanding of PDAC biology [1], developments in pre-operative imaging [2], adjuvant/neoadjuvant chemotherapy [3,4], and image-guided surgery [5], there have been only marginal improvements in survival over the last two decades [6,7]. Resection of PDAC with clear surgical margins (R0) [8,9]. A significant proportion of patients present with advanced disease and so the development of diagnostic tests to identify pre-malignant or early-stage PDAC is vital. PDAC develops through the step-wise accumulation of mutations in tumour suppressor and oncogenes [12] accompanied by histological progression from benign precursor lesions (PanIN) to invasive malignancy and metastases [13,14]. Mutations in the Kirsten Rat Sarcoma (KRAS) oncogene are Cancers 2020, 12, 2353; doi:10.3390/cancers12092353 www.mdpi.com/journal/cancers
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