Again, the Caspase pathway serum levels of miR-196a and miR-196b were significantly higher in patients with sporadic and familial PC and
IAR with multifocal PanIN2/3 lesions than in patients with pNENs, CP, and PanIN1 lesions and healthy controls ( Figure 2 and Table 2). miRNA levels were highest (up to 46-fold) in patients with metastasized PC stage IV (n = 10). miR-196a had a sensitivity of 1 and a specificity of 0.6 (AUC = 0.64) for the discrimination between normal and PanIN2/3 ( Figure 3), as well as 0.9 and 0.89 (AUC = 0.97) for the discrimination between normal and PC, respectively. miR-196b had a sensitivity and a specificity of 1 each (AUC = 1.0) for the discrimination between normal and PanIN2/3 ( Figure 3) and a sensitivity of 1 and a specificity of 0.78 (AUC = 0.86) for the discrimination between normal and PC. The combination of both miR-196a and miR-196b attained the best discrimination between control and either multifocal PanIN2/3 (a sensitivity of 1 and a specificity of 1) or sporadic invasive PC (a sensitivity of 1 and a specificity of 1). The
results of miR-196a and -196b ROC curves are presented in Table 2. A ∆Ct value of 7.51 Pembrolizumab manufacturer for miR-196a and a ∆Ct value of 6.35 for miR-196b were calculated as cutoff values that indicate the presence of high-grade PanIN2/3 lesions or PC. Interestingly, in nine PC patients with available preoperative and Branched chain aminotransferase early postoperative serum samples, the preoperative elevated miR-196a and miR-196b dropped to the normal range after potential curative resection. The same was true for the five IAR with multifocal PanIN2/3 lesions (Figure 4, A and B). Consensus statements recommend screening IAR of FPC families with endoscopic ultrasonography and MRI, as these are considered to be the best imaging modalities [12] and [34]. However, these tools often fail to reliably detect high-grade lesions (PanIN3)
and early PC. In addition, up to 40% of IAR show small cystic lesions on imaging that might represent small branch-duct type IPMNs [34]. It was suggested that these lesions are a surrogate for the presence of non-visible, high-grade PanIN lesions somewhere else in the pancreas of the IAR [14]. Thus, biomarkers that reliably indicate the presence of high-grade PanIN or early PC lesions would be of great value for the screening of IAR in the setting of FPC and could lead to curative resection. Several miRNAs can potentially serve as such biomarkers as these are reported to be upregulated in PC [27], PanINs [35], and IPMNs [28]. A recent meta-analysis of nine studies, including four with serum analysis, evaluating 20 miRNAs in 941 patients with PC calculated a pooled sensitivity of 0.
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