1644P - The mutation landscape and evolution pattern of liver or peritoneal metastasis in pancreatic cancer

Background

Pancreatic ductal adenocarcinoma (PDAC) has been found to metastasize in more than 50% of patients at the time of their initial diagnosis. This is considered to be the main reason for mortality. The liver and peritoneum are frequently observed as metastatic locations in cases of PDAC. The mutational profile and evolutionary patterns of metastatic lesions in the liver and peritoneum in pancreatic cancer remain poorly understood.

Methods

Whole exome sequencing (WES) was performed on 47 samples from 30 treatment-naïve, synchronously resected hepatic or peritoneal metastatic PDACs. The present study examined 10 primary tumours that did not metastasize within a year after surgery (non-PTs), 8 matched pairs of liver-metastatic primary (LiM-PTs) and metastatic (LiM-MTs), 9 matched pairs of peritoneal-metastatic primary (PeM-PTs), and 3 unpaired primary and metastatic tumours.

Results

KRAS mutations were found in 89.65% (26/29) of primary tumours, 70% (7/10) of liver metastases, and 100% (8/8) of peritoneal metastases. Interestingly, PCDHB14 and PXDN mutations were only detected in non-PTs, MUC16 were only detected in LiM-PTs, and ZNF594 were only detected in PeM-PTs, although there was no statistical difference. Meanwhile, the LiM-MTs group had higher TMB than PeM-MTs group (P=0.048). Mutation pattern analysis found that transitions outnumbered transversions in all samples. The paired LiM-PTs and PeM-PTs samples underwent GO and KEGG analyses. The ECM-receptor interaction signaling pathway that has been linked to metastasis in other cancer types was found to be distinct in LiM-PTs as compared to other groups. On the other hand, the proteoglycans and calcium signaling pathway was found to be unique to LiM-MTs when compared to PeM-MTs. Phylogenetic relationships analysis found that neither the LiM group nor the PeM group has a unified evolutionary pattern.

Conclusions

This research reveals that PDAC liver metastasis and peritoneal metastasis differ in mutated genes and evolutionary pattern. These results suggest that different biological mechanisms may exist in metastasis to different sites, and also highlights the need for more precise personalized treatment for PDAC in clinical practice.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The first affiliated hospital of Henan university of science and technology.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.