Mutated KRAS is considered as a negative prognostic marker for survival in pancreatic ductal adenocarcinoma (PDAC). However, prognostic values of individual mutations (G12D, G12V or G12R) are still controversial. The aim of current study was to evaluate the survival of pancreatic cancer patients with different subtypes of KRAS mutations.
Tumor tissue was obtained from 109 patients (pts) with PDAC stage I-IV (stage I – 6 pts, stage II – 27 pts, stage III – 19 pts, stage IV – 57 pts) treated at the N.N. Alexandrov National Cancer Centre of Belarus in 2019. To investigate KRAS mutations (G12D, G12V, G12R) polymerase chain reaction with TaqMan probes was performed. Statistics: exact Fisher’s test, Log-rank test.
KRAS mutations were detected in 69% of samples. The distribution of different subtypes of KRAS mutations was: G12D 47%, G12V 40%, G12R 13%. Patients with stage II PDAC received chemotherapy more often in KRAS-mut group than in wild type PDAC (WT) (70% vs 33%; p<0,05). There were no significant differences in sex, age, stage distribution, and surgical resection rate depending on KRAS status. KRAS-mut PDAC more frequently located in the head of the pancreas (47% vs 26%; p=0,06) than WT. G12V PDAC had lymph node involvement more frequently than WT (96% vs 66%, p<0,01) or G12R (96% vs 55%, p<0,01). Lung metastasis were not detected at diagnosis in patients with G12V metastatic PDAC. In other groups (KRAS-mut, WT, G12D, G12R) lung metastasis frequency varied from 11% to 29%. There was no statistical difference in overall survival (OS) between any of KRAS groups and WT in stages I-II and III-IV PDAC. Median OS was significantly different between G12R and G12D unresectable PDAC stages III-IV (322 days vs 104 days; p<0,05). One-year survival rate for pts with PDAC stages III-IV was better in WT group than G12D (33% vs 5%; p<0,05). Chemotherapy was significantly associated with better OS in pts with unresectable PDAC stages III-IV in WT, KRAS-mut and G12D groups (p<0,01) but not in G12V (p=0,5).
We found no significant association between mutated KRAS and OS in PDAC pts, possibly due to a small sample size. However, pts with G12D mutation had worse one-year survival rate and lower OS than pts with other subtypes of KRAS mutation.
Legal entity responsible for the study
N.N. Alexandrov National Cancer Centre of Belarus.
Belarusian Republican Foundation of Fundamental Research.
All authors have declared no conflicts of interest.