Comparison of Comprehensive Serum miRNA Sequencing and Apolipoprotein A2 Isoforms for Early Detection of Pancreatic...

Pancreatic cancer is frequently diagnosed at advanced stages, highlighting the need for biomarkers that are capable of detecting early-stage disease in asymptomatic individuals. Recently, apolipoprotein A2 isoforms (ApoA2-ATQ/AT) have been reported as a new blood biomarker for pancreatic cancer. We recently developed diagnostic models based on 100 highly expressed serum microRNAs (miRNAs) combined with CA19-9; these models achieved high accuracy in terms of distinguishing individuals with pancreatic cancer from healthy individuals. This study aimed to compare the diagnostic performance of these miRNA-based models with that of the ApoA2-ATQ/AT biomarker.

Comprehensive sequencing of serum miRNAs was conducted using samples from 120 pancreatic cancer patients recruited across 14 hospitals, along with 93 healthy controls without cancer. Serum CA19-9 levels, miRNA index values, miRNA+CA19-9 index values, and ApoA2 index values were assessed. miRNA-based indices were derived from classification models built on an automated machine-learning platform.

The miRNA model (AUC 0.94; 95% CI 0.91-0.97) and the miRNA+CA19-9 model (AUC 0.99; 95% CI 0.98-1.00) outperformed ApoA2 (AUC 0.89; 95% CI 0.84-0.93) in terms of distinguishing individuals with pancreatic cancer from healthy controls across all stages. In early-stage disease (stages 0-I and 0-II), both miRNA-based models also demonstrated superior performance. Strong negative correlations were observed between the ApoA2 index and both the miRNA model index (r = -0.62) and the miRNA+CA19-9 index (r = -0.63).

These findings suggest that miRNA-based diagnostic models, particularly when combined with CA19-9, could serve as powerful tools for the early detection of pancreatic cancer.