The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient’s blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.

Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients

“…Previous studies have reported several predictive markers for risk estimation, such as S100P, ERO1LB, SULF1, ITGA2, GPRC5A, ACTN4, LMO2, p16INK4a, CLPS, COL11A1, GJB2, CTRL, CEL, CPA1, POSTN, PM20D1, and MARCO (Lin et al 2020 ; Jiang et al 2018 ; Wang et al 2020 ; Ho et al 2020 ; Watanabe et al 2015 ; Nakata et al 2009 ; Shi et al 2021 ; Gerdes et al 2002 ; Lyu et al 2018 ; Zhang et al 2013 ; Ji et al 2014 ). Furthermore, many miRNAs also demonstrate prognostic roles in PCs (Khan et al 2015 ; Eid et al 2021 ). It is noteworthy that most existing prognostic models for PC involve only one gene or are only related to short-term clinical response (DFS) or long-term clinical effects (OS).…”

Current Screening Strategies for Pancreatic Cancer

“…The marker maintains a sensitivity of 79–81% and a specificity of 82–90% for the diagnosis of PDAC in symptomatic patients [ 82 , 83 ], and its elevation signifies advanced disease and poor prognosis [ 84 , 85 , 86 ]. However, as PDAC is usually asymptomatic at the early stage, the positive predictive value of CA 19-9 is only 0.9% in this setting [ 87 , 88 ]. Zubarik and colleagues recorded elevated CA 19-9 in 4.9% (n = 27) of subjects in their screening study involving 546 HRIs; neoplastic findings were identified in five individuals on subsequent EUS, and PDAC was diagnosed in one patient (0.2%) [ 89 ].…”

“…More recently, novel blood-based biomarkers for early diagnosis have made progress. Studies have confirmed that abnormally expressed serum microRNAs (miRNAs) have certain significance in the diagnosis of early-stage PDAC, or even in precancerous pancreatic lesions [ 88 , 96 ]. The diagnostic value of miRNAs was shown to be higher than that of conventional serum markers [ 97 ], and there is evidence that the combination of miRNAs and CA19-9 is more accurate [ 98 , 99 ].…”

Current trends in the diagnosis of pancreatic cancer

“…The marker maintains a sensitivity of 79-81% and specificity of 82-90% for the diagnosis of PDAC in symptomatic patients (19,39), and its elevation signifies advanced disease and poor prognosis (40)(41)(42). However, as PDAC is usually asymptomatic at the early stage, the positive predictive value of CA 19-9 is only 0.9% in this setting (43,44). Furthermore, the elevation of CA 19-9 can also be caused by other conditions, including benign diseases (pancreatitis, cirrhosis, biliary obstruction, and acute cholangitis) (45)(46)(47) and different malignancies (colorectal, gastric, and uterine cancers) (38).…”