KRAS Mutant Allele Fraction in Circulating Cell-Free DNA Correlates With Clinical Stage in Pancreatic Cancer Patients

Abstract

Background: The research on circulating tumor DNA (ctDNA) in pancreatic cancer (PC) has emerged recently. Although the detection rate of the KRAS mutation in ctDNA was relatively consistent with that in tumor tissue, whether the KRAS mutant allele fraction (MAF) differed was still not reported. So far, the clinical application of ctDNA detection in PC remains inconclusive.Methods: Plasma samples were collected from 110 PC and 52 pancreatic benign (PB) disease patients. The detection of KRAS mutation in ctDNA was performed using droplet digital PCR and compared with that in matched tumor tissue. We assessed the utility of KRAS MAFs in ctDNA and tissue for pancreatic malignancy assessment.Results: We found that KRAS MAF in ctDNA of PC patients was higher than that of PB patients, and was obviously associated with tumor staging and distant metastasis. However, KRAS MAF in ctDNA was significantly different from that in matched tissue. KRAS MAF in tumor tissue had no significant correlation with the clinical status. In addition, a ROC curve analysis revealed that mutant KRAS ctDNA combined with CA19-9 could increase the sensitivity rate of early-stage PC prediction, compared with CA19-9 test alone.Conclusion: The MAF of KRAS in ctDNA was related to the clinical stage of PC (p = 0.001). Mutant KRAS ctDNA could improve the sensitivity in early diagnosis of PC as a complement to CA19-9. Our study suggested that KRAS mutation in ctDNA could be a valuable circulating biomarker for the malignancy assessment in PC.

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer

“…RAS mutation was detected in 76.7% (33/43) of tissue samples and in 77% (47/61) of basal plasma samples. The percentage of patients with RAS mutation was comparable to other cohort studies [ 11 , 12 , 13 ]. Mutation in codon 12 of the KRAS gene was found in 93.6% (44/47), and 93.9% (31/33) of plasma and tissue samples, respectively ( Table S1 ).…”

“…In fact, the prognosis was more accurately predicted by RAS mutation analysis in cfDNA than in tissue. The allelic ratio and dosage of mutated KRAS may impact on PDAC biology [ 18 ], and KRAS MAF in cfDNA has been found to correlate with clinical stage and outcome in PDAC [ 13 , 19 ]. In this regard, our results reveal that circulating KRAS MAF in cfDNA predicted survival in metastatic PDAC patients.…”

Computer-Aided Diagnosis and Staging of Pancreatic Cancer Based on CT Images

“…Content may change prior to final publication. Citation information: DOI 10.1109/ACCESS.2020.3012967, IEEE Access resection [36]; therefore, in this paper, stage I and stage II are collectively referred to as early stage [16,[37][38][39][40].…”

The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis

“…However, the detection of circulating KRAS-mutant cfDNA has a sensitivity for the diagnosis of PDAC of only 20–25% [ 21 , 22 ]. This may result from the relatively low mutant allele fraction seen in PDAC [ 23 ], or because a PDAC needs to be relatively advanced before sufficient mutant DNA is released into the circulation. Sampling of pancreatic exocrine secretions may offer higher sensitivity because PDAC originates from the ductal epithelium and therefore mutant KRAS might be expected to be present in pancreatic secretions earlier in PDAC evolution than the point at which it enters the blood.…”