Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) of the head (H) and body/tail (B/T) differ in embryonic origin, cell composition, blood supply, lymphatic and venous drainage, and innervation. We aimed to compare the molecular and tumor immune microenvironment (TIME) profiles of PDAC of the H vs. B/T.
Methods: A total of 3499 PDAC samples were analyzed via next-generation sequencing (NGS) of RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Significance was determined as p values adjusted for multiple corrections (q) of < 0.05.
Results: Anatomic subsites of PDAC tumors were grouped by primary tumor sites into H (Nf2058) or B/T (Nf1384). There were significantly more metastatic tumors profiled from H vs. B/T (57% vs. 44%, p0.05). Expression analysis of IO-related genes showed significantly higher expression of CTLA4 and PDCD1 in H (q< 0.05, fold change 1.2 and 1.3) and IDO1 and PDCD1LG2 expression trended higher in B/T (p< 0.05, fold change 0.95).
Conclusion: To our knowledge, this is one of the largest cohorts of PDAC tumors subjected to broad molecular profiling. Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.
Methods: A total of 3499 PDAC samples were analyzed via next-generation sequencing (NGS) of RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Significance was determined as p values adjusted for multiple corrections (q) of < 0.05.
Results: Anatomic subsites of PDAC tumors were grouped by primary tumor sites into H (Nf2058) or B/T (Nf1384). There were significantly more metastatic tumors profiled from H vs. B/T (57% vs. 44%, p0.05). Expression analysis of IO-related genes showed significantly higher expression of CTLA4 and PDCD1 in H (q< 0.05, fold change 1.2 and 1.3) and IDO1 and PDCD1LG2 expression trended higher in B/T (p< 0.05, fold change 0.95).
Conclusion: To our knowledge, this is one of the largest cohorts of PDAC tumors subjected to broad molecular profiling. Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.
| Original language | English (US) |
|---|---|
| Pages (from-to) | S625 |
| Journal | HPB |
| Volume | 26 |
| DOIs | |
| State | Published - 2024 |