RNA-SEQUENCING OF PANCREATIC CANCER FROM EUS-ACQUIRED TISSUE IS USEFUL TO DEFINE MOLECULAR SUBTYPES AND PROGNOSIS

Aims Pancreatic ductal adenocarcinoma (PDAC) is the 2^nd leading cause of cancer-related mortality, with transcriptome subtypes related to different prognosis and chemotherapy response.

Nevertheless, RNA extraction from pancreatic tissue is cumbersome and has been performed mainly on surgical samples, representative of<20% of cases. On the contrary, the majority of PDAC patients undergo Endoscopic UltraSound(EUS)-guided tissue acquisition(EUS-TA), and we recently published a method to achieve a good quality and quantity RNA, but RNAsequencing on such samples has been rarely performed.

Our aim was to evaluate the ability to perform RNAsequencing and molecular subtype identification on EUS-TA of PDAC samples and correlate this to prognosis and chemotherapy response.

Methods Fifteen patients with non-metastatic PDAC underwent EUS-TA with standard FNA and resulted having adequate quantity of RNA(70 ng) and RNA Integrity Index(RIN)≥3 for RNAsequencing with Illumina Nova-Seq. Unsupervised clustering according to selected markers known to be associated to molecular subtypes and evaluated through in silico analysis of TCGA, as also the PURIST score were applied and correlated to overall survival (OS) and chemotherapy used. Further bioinformatics analysis and correlation with clinical metadata and overall survival are ongoing.

Results Mean RIN of the 15 samples was 4.7(range 3-6), OS 11 months. RNAsequencing was successful in 100% patients. Unsupervised clustering employing relevant genes was applied and correlated to OS; PURIST score identified 1 patient as basal-like, who had an OS of 3 months.

Conclusions RNA samples obtainable from EUS-TA PDAC cases can successfully undergo RNAsequencing to identify molecular subtypes that seem to correlate with prognosis and chemotherapy response.

Publication History

Article published online:
14 April 2022