A basal-like pancreatic cancer molecular subtype can be identified on EUS-acquired tissue and is associated to current smoking, lower Ca19.9 expression and worse prognosis

Aims Two pancreatic cancer(PDAC) transcriptome subtypes have been defined (basal-like and classical) that seem related to different prognosis. Nevertheless, RNA-extraction from pancreatic tissue is cumbersome and has been performed mainly on surgical samples, representative of<20% of cases. Most PDAC patients undergo Endoscopic-UltraSound(EUS)-guided tissue acquisition(EUS-TA), but RNA-sequencing on such samples has been rarely performed or limited to paraffin-embedded samples with low RNA quality. Furthermore, the association between molecular subtype and patient-related factors such as BMI, smoking, drug use, tumor location and Ca19.9 expression is uninvestigated. Our aim was to correlate PDAC molecular subtypes identified by RNA-sequencing on EUS-TA samples with prognosis and evaluate whether they are associated to patients’ factors.

Methods Consecutive patients with non-metastatic PDAC who underwent EUS-TA at diagnosis were enrolled in a prospective biobanking study with snap-frozen samples. Those with adequate quantity and quality of RNA underwent RNA-sequencing with Illumina Nova-Seq. PURIST score was applied to define transcriptional subtype and association with patient-related factors and overall survival (OS) investigated. Categorical and continuous variables were investigated by Fisher’s exact test or Mann-Whitney test, correlation analyses with Pearson test.

Results In 44/45 samples, RNA was of quantity and integrity allowing successful RNA-sequencing. According with PURIST score 3 patients were classified as basal-like (6.8%) and the other 41 as classical. Basal-like patients had a significantly lower median OS compared to classical (3 vs 16 months; p=0.01) and a basal-like phenotype was associated to increased risk of death (HR 7.79; p=0.006). PURIST score also significantly correlated inversely with OS (r=-0.6; p=0.0007). Concerning patients’ variables, patients with basal-like tumors were more frequently current smokers (66.6% vs 12.2%; p=0.05) and had a lower baseline Ca19.9 (80 vs 1243 IU/ml; p=0.001). No differences were found concerning age, gender, BMI, diabetes history, disease stage, tumor location, use of aspirin or statins.

Conclusions Molecular subtype identification on EUS-TA PDAC cases at diagnosis is feasible and a basal-like phenotype is rare but associated to worse prognosis. Furthermore, current smoking seems to be associated to a more aggressive molecular subtype, which in turn does not seem to express a high Ca19.9. Further studies on a larger cohort are needed to confirm such findings.

Publication History

Article published online:
15 April 2024