Head and Body/Tail Pancreatic Carcinomas Are Not the Same Tumors

The association between pancreatic ductal adenocarcinoma (PDAC) location (head vs. Body/Tail (B/T)) and clinical outcome remains controversial. We collected clinicopathological and gene expression data from 249 resected PDAC samples from public data sets, and we compared data between 208 head and 41 B/T samples. The 2-year overall survival (OS) was better for the head than for the B/T PDACs (44 vs. 27%, p = 0.043), especially when comparing tumors with similar TNM classification (T3/4N0M0: 67% vs. 17%, p = 0.002) or from the same molecular class (squamous subtype: 31% vs. 0%, p &lt
0.0001). Bailey&rsquo
s molecular subtypes were differentially distributed within the two groups, with the immunogenic subtype being underrepresented in the &ldquo
B/T&rdquo
group (p = 0.005). Uni- and multivariate analyses indicated that PDAC anatomic location was an independent prognostic factor. Finally, the supervised analysis identified 334 genes differentially expressed. Genes upregulated in the &ldquo
head&rdquo
group suggested lymphocyte activation and pancreas exocrine functions. Genes upregulated in the &ldquo
group were related to keratinocyte differentiation, in line with the enrichment for squamous phenotype. We identified a robust gene expression signature (GES) associated with B/T PDAC location, suggesting that head and B/T PDAC are different. This GES could serve as an indicator for differential therapeutic management based on PDAC location.