FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4206566745> ?p ?o ?g. }

• W4206566745 endingPage "598" @default.
• W4206566745 startingPage "598" @default.
• W4206566745 abstract "598 Background: PDAC of the H and B/T differ in embryonic origin, cell composition, blood supply, lymphatic and venous drainage, and innervation. H tumors tend cause symptoms earlier and to present at earlier stages compared to B/T cancers. The impact of PDAC tumor location on patient presentation and survival has been shown in large national data-based analyses, although with conflicting results. 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 (IHC, Caris Life Sciences, Phoenix, AZ). RNA deconvolution was performed using QuantiSeq (Finotello 2019, Genome Medicine) to quantify the immune cell infiltration. Pathway gene enrichment analyses were done using Gene Set Enrichment Analysis (GSEA, Subramaniam 2015, PNAS). Significance was determined as p values adjusted for multiple correction (q) of < 0.05. Results: Anatomic subsites of PDAC tumors were grouped by primary tumor sites into H (N = 2058) or B/T (N = 1384). There were significantly more metastatic tumors profiled from H vs. B/T (57% vs. 44%, p < 0.001). KRAS mutations (93.8% vs. 90.2%), genomic loss of heterozygosity (12.7% vs. 9.1%), and several copy number alterations ( FGF3, FGF4, FGF19, CCND1, ZNF703, FLT4, MUTYH, TNFRS14) trended higher in B/T when compared to H (p < 0.05 but q > 0.05). GNAS mutations (2.2% vs. 0.7%) trended higher in H vs. B/T (p < 0.05). No significant difference in immuno-oncology (IO) markers (TMB, PD-L1, MSI-H) were observed, but 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). When comparing median cell abundance values as part of TIME analysis, H had increased immune infiltration of B cells (0.045 vs. 0.043), M2 macrophages (0.035 vs. 0.032), neutrophils (0.056 vs. 0.052), NK cells (0.027 vs. 0.026), CD8+ T cells (% > 0: 48.2% vs. 43.2%), while B/T had increased infiltration of M1 macrophages (0.035 vs. 0.032) (all q < 0.05). GSEA showed enrichment of CTLA4 (normalized enrichment score (NES) 1.6, false discovery rate (FDR) 0.19) and primary immunodeficiency pathway enrichment (NES 1.7, FDR 0.11) in H. Conclusions: To our knowledge, this is one of the largest cohort 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 profliles of H vs. B/T tumors were also observed." @default.
• W4206566745 created "2022-01-25" @default.
• W4206566745 creator A5006538210 @default.
• W4206566745 creator A5040325455 @default.
• W4206566745 creator A5055915497 @default.
• W4206566745 creator A5061883893 @default.
• W4206566745 creator A5062667375 @default.
• W4206566745 creator A5071826146 @default.
• W4206566745 creator A5072203753 @default.
• W4206566745 creator A5080544645 @default.
• W4206566745 creator A5088223962 @default.
• W4206566745 date "2022-02-01" @default.
• W4206566745 modified "2023-09-23" @default.
• W4206566745 title "Comparative molecular profiling of pancreatic ductal adenocarcinoma (PDAC) of the head (H) versus body/tail (B/T) and the tumor immune microenvironment (TIME)." @default.
• W4206566745 doi "https://doi.org/10.1200/jco.2022.40.4_suppl.598" @default.
• W4206566745 hasPublicationYear "2022" @default.
• W4206566745 type Work @default.
• W4206566745 citedByCount "0" @default.
• W4206566745 crossrefType "journal-article" @default.
• W4206566745 hasAuthorship W4206566745A5006538210 @default.
• W4206566745 hasAuthorship W4206566745A5040325455 @default.
• W4206566745 hasAuthorship W4206566745A5055915497 @default.
• W4206566745 hasAuthorship W4206566745A5061883893 @default.
• W4206566745 hasAuthorship W4206566745A5062667375 @default.
• W4206566745 hasAuthorship W4206566745A5071826146 @default.
• W4206566745 hasAuthorship W4206566745A5072203753 @default.
• W4206566745 hasAuthorship W4206566745A5080544645 @default.
• W4206566745 hasAuthorship W4206566745A5088223962 @default.
• W4206566745 hasConcept C104317684 @default.
• W4206566745 hasConcept C121608353 @default.
• W4206566745 hasConcept C126322002 @default.
• W4206566745 hasConcept C142724271 @default.
• W4206566745 hasConcept C150194340 @default.
• W4206566745 hasConcept C162317418 @default.
• W4206566745 hasConcept C203014093 @default.
• W4206566745 hasConcept C2776107976 @default.
• W4206566745 hasConcept C2778740770 @default.
• W4206566745 hasConcept C2779013556 @default.
• W4206566745 hasConcept C2781187634 @default.
• W4206566745 hasConcept C502942594 @default.
• W4206566745 hasConcept C526805850 @default.
• W4206566745 hasConcept C54355233 @default.
• W4206566745 hasConcept C71924100 @default.
• W4206566745 hasConcept C86803240 @default.
• W4206566745 hasConcept C8891405 @default.
• W4206566745 hasConceptScore W4206566745C104317684 @default.
• W4206566745 hasConceptScore W4206566745C121608353 @default.
• W4206566745 hasConceptScore W4206566745C126322002 @default.
• W4206566745 hasConceptScore W4206566745C142724271 @default.
• W4206566745 hasConceptScore W4206566745C150194340 @default.
• W4206566745 hasConceptScore W4206566745C162317418 @default.
• W4206566745 hasConceptScore W4206566745C203014093 @default.
• W4206566745 hasConceptScore W4206566745C2776107976 @default.
• W4206566745 hasConceptScore W4206566745C2778740770 @default.
• W4206566745 hasConceptScore W4206566745C2779013556 @default.
• W4206566745 hasConceptScore W4206566745C2781187634 @default.
• W4206566745 hasConceptScore W4206566745C502942594 @default.
• W4206566745 hasConceptScore W4206566745C526805850 @default.
• W4206566745 hasConceptScore W4206566745C54355233 @default.
• W4206566745 hasConceptScore W4206566745C71924100 @default.
• W4206566745 hasConceptScore W4206566745C86803240 @default.
• W4206566745 hasConceptScore W4206566745C8891405 @default.
• W4206566745 hasIssue "4_suppl" @default.
• W4206566745 hasLocation W42065667451 @default.
• W4206566745 hasOpenAccess W4206566745 @default.
• W4206566745 hasPrimaryLocation W42065667451 @default.
• W4206566745 hasRelatedWork W11626209 @default.
• W4206566745 hasRelatedWork W2232434 @default.
• W4206566745 hasRelatedWork W22506665 @default.
• W4206566745 hasRelatedWork W2482010 @default.
• W4206566745 hasRelatedWork W25273801 @default.
• W4206566745 hasRelatedWork W2773312 @default.
• W4206566745 hasRelatedWork W30070566 @default.
• W4206566745 hasRelatedWork W3477638 @default.
• W4206566745 hasRelatedWork W4892554 @default.
• W4206566745 hasRelatedWork W7190444 @default.
• W4206566745 hasVolume "40" @default.
• W4206566745 isParatext "false" @default.
• W4206566745 isRetracted "false" @default.
• W4206566745 workType "article" @default.