Abstract
Pancreatic cancer (PC) is regarded as one of the most lethal malignant diseases in the world, with GLOBOCAN 2020 estimates indicating that PC was responsible for almost half a million deaths worldwide in 2020. Pancreatic cystic lesions (PCLs) are fluid-filled structures found within or on the surface of the pancreas, which can either be pre-malignant or have no malignant potential. While some PCLs are found in symptomatic patients, nowadays many PCLs are found incidentally in patients undergoing cross-sectional imaging for other reasons-so called 'incidentalomas'. Current methods of characterising PCLs are imperfect and vary hugely between institutions and countries. As such, there is a profound need for improved diagnostic algorithms. This could facilitate more accurate risk stratification of those PCLs that have malignant potential and reduce unnecessary surveillance. As PC continues to have such a poor prognosis, earlier recognition and risk stratification of PCLs may lead to better treatment protocols. This review will focus on the importance of biomarkers in the context of PCLs and PCand outline how current 'omics'-related work could contribute to the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC.
Highlights
Pancreatic cancer can be divided into two main subtypes: pancreatic adenocarcinoma, which is responsible for 85–90% of all pancreatic neoplasms and has a five-year survival rate of just 8%, and pancreatic neuroendocrine tumour (PanNET), which is far less common and represents less than 5% of PC [1,3,4]
A recent study conducted by Ding et al indicated a negative correlation with tumorigenesis in intraductal papillary mucinous neoplasms (IPMNs) for CTD-2033D15.2 and HAND2-AS1, while a positive correlation was observed for long non-coding RNAs (lncRNAs)-TFG [41]. These results suggest a protective role of HAND2-AS1 and CTD-2033D15.2 expression in IPMNs, while lncRNA-TFG appears as a risk factor for tumorigenesis in IPMNs [41]
Vila-Navarro et al used next-generation sequencing (NGS) to conduct genome-wide miRNA profiling and identified 30 independent miRNAs whose expression is significantly increased in PC and IPMN lesions compared to healthy individuals, and these results were validated in two independent sample sets [78]
Summary
Von Hippel–Lindau (VHL) disease, caused by a germline mutation to the VHL tumour-suppressor gene, is associated with an increased risk of pancreatic neuroendocrine tumours and non-malignant serous-type PCLs [11]. One of the most significant risk factors for PCLs is age, with patients typically being diagnosed at 50 years or older and the incidence rate rising exponentially with age thereafter [6,7,8,12]. A 2017 study showed a positive correlation between socioeconomic development (measured through Human Development Index and Gross Domestic Product) and pancreatic cancer incidence and mortality [15] This observed increase in PC incidence with rising socioeconomic development is thought to be result of the Western lifestyle and ageing population, which are known to be large risk factors of PC [15]. With the rising prevalence of PCLs globally and poor survival rates associated with PC, there is a great need for improved characterisation of pre-malignant PCLs to allow surgery in those who need it, while avoiding unnecessary surveillance and intervention in those who do not
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