AUTHOR=Wang Zhe-Ying , Ding Xiao-Qing , Zhu Hui , Wang Rui-Xian , Pan Xiao-Rong , Tong Jian-Hua 

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

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01295

DOI=10.3389/fonc.2019.01295

ISSN=2234-943X

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