Kras Gene Analysis Using Liquid-Based Cytology Specimens Predicts Therapeutic Responses and Prognosis in Patients with Pancreatic Cancer

SIMPLE SUMMARY: New therapeutic strategies are needed to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC) and developing biomarkers that can guide individualized treatment decisions is an important part of these strategies. In this study, we found that unresectable PDAC patients harboring wild-type Kras had significantly longer progression-free survival (PFS) and overall survival (OS) than those harboring mutant Kras after undergoing first-line gemcitabine and nab-paclitaxel (GA) therapy and that wild-type Kras was a significant predictor of longer PFS and OS. This is the first report suggesting that Kras gene analysis has the potential to predict therapeutic responses to GA and the prognosis of unresectable PDAC. ABSTRACT: Background: Although several molecular analyses have shown that the Kras gene status is related to long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC), the results remain controversial. Here, we examined the Kras gene status in a cohort of unresectable PDAC patients who underwent first-line therapy with gemcitabine and nab-paclitaxel (GA) and assessed differences in chemotherapy responses and survival. Methods: Patients with a histological diagnosis of PDAC (based on EUS-guided fine-needle aspiration) from 2017 to 2019 were enrolled. Tumor genomic DNA was extracted from residual liquid-based cytology specimens and Kras mutations were assessed using the quenching probe method. The relationships between the Kras status and progression-free survival (PFS) and overall survival (OS) were assessed. Results: Of the 110 patients analyzed, 15 had wild-type Kras. Those with the wild-type gene showed significantly longer PFS and OS than those with mutant Kras (6.9/5.3 months (p = 0.044) vs. 19.9/11.8 months (p = 0.037), respectively). Multivariate analyses identified wild-type Kras as a significant independent factor associated with longer PFS and OS (HR = 0.53 (p = 0.045) and HR = 0.35 (p = 0.007), respectively). Conclusions: The analysis of the Kras gene status could be used to predict therapeutic responses to GA and prognosis in unresectable PDAC patients.