Abstract
Abstract 7615: Epithelial-mesenchymal-transition gene signature changes and poor oncological outcome in Candida -positive pancreatic ductal adenocarcinoma
Cancer research (Chicago, Ill.), Vol.84(6_Supplement), pp.7615-7615
03/22/2024
DOI: 10.1158/1538-7445.AM2024-7615
Abstract
Abstract Candida are commonly found in bile collected during surgery in pancreatic ductal adenocarcinoma (PDAC) patients. However, their significance in tumor biology and oncological outcome is unclear. PDAC patients receiving neoadjuvant therapy and pancreatectomy with intraoperative bile fungal culture were identified (N=40) in a prospective single-institution cohort. Tumor regression scores (TRS) were abstracted from pathology reports and correlated with bile fungal cultures. Bulk tumor RNASeq data were obtained from the Oncology Research Information Exchange Network (ORIEN). Tumor microbiome data of non-metastatic PDAC patients with upfront surgery were extracted using the {exotic} tool (Hoyd et al. Cancer Res. Commun., 2023). Gene expression profiles were compared between Candida+ and Candida- tumors, defined by a cutoff microbial count of 0. Overall survival (OS) of resected PDAC patients with Candida+ and Candida- tumors was compared using Kaplan Meier survival analysis. From the single-institution PDAC cohort, Candida+ bile was associated with poor pathological response to neoadjuvant therapy (Table 1). Using the ORIEN cohort, Candida were detected in 67% (106/158) of the PDAC tumors. Patients with Candida+ tumors had worse OS (median 28 vs. 56 months, Log-Rank p<0.008). Gene Set Enrichment Analysis (GSEA) using Hallmark gene sets showed an enrichment of epithelial-mesenchymal-transition (EMT) gene set and a reduction of metabolic and DNA repair gene sets in Candida+ tumors. GSEA for Immune signature and Tumor Immune Microenvironment Deconvolution (TIMEx) cell types showed an enrichment of Stromal-Fibroblast and EMT signature in Candida+ tumors. Further investigations are underway to determine the causal and metabolic relationship between Candida and this tumor microenvironment with EMT and stromal fibroblasts which is a well-known contributor to poor chemotherapy response and oncological outcome of PDAC. Table 1: Pathological Response to Neoadjuvant Therapy for PDAC Bile Culture TRS0/1 TRS2 TRS3 Candida - 5 (25%) 15 (75%) 0 (0%) Candida + 1 (5%) 11 (55%) 8 (40%) TRS: Tumor Regression Score (TRS0: complete response; TRS1: near-complete response; TRS2: partial response; TRS3: no response). Chi-Square Test, P=0.0035. Citation Format: Po Hien Ear, Min Hu, Jonathan S. Shilyansky, Naomi H. Fei, Sam Coleman, Rebecca Hoyd, Caroline E. Wheeler, Kelsey L. Steckly, Michelle L. Churchman, Nicholas Denko, Rebecca D. Dodd, Sheetal Hardikar, Ning Jin, Qin Ma, Martin D. McCarter, Abdul Rafeh Naqash, Afaf E. Osman, Gregory Riedlinger, Lary A. Robinson, Bryan P. Schneider, Eric A. Singer, Ahmad A. Tarhini, Gabriel Tinoco, Cornelia M. Ulrich, Yousef Zakharia, Daniel Spakowicz, Aik Choon Tan, Carlos H. Chan. Epithelial-mesenchymal-transition gene signature changes and poor oncological outcome in Candida-positive pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7615.
Details
- Title: Subtitle
- Abstract 7615: Epithelial-mesenchymal-transition gene signature changes and poor oncological outcome in Candida -positive pancreatic ductal adenocarcinoma
- Creators
- Po Hien Ear - University of IowaMin Hu - Huntsman Cancer InstituteJonathan S. ShilyanskyNaomi H. Fei - University of IowaSam Coleman - Huntsman Cancer InstituteRebecca Hoyd - The Ohio State UniversityCaroline E. Wheeler - The Ohio State UniversityKelsey L. Steckly - University of IowaMichelle L. ChurchmanNicholas Denko - The Ohio State UniversityRebecca D. Dodd - University of IowaSheetal Hardikar - Huntsman Cancer InstituteNing Jin - The Ohio State UniversityQin Ma - The Ohio State UniversityMartin D. McCarter - University of Colorado DenverAbdul Rafeh Naqash - University of OklahomaAfaf E. Osman - University of UtahGregory Riedlinger - Rutgers, The State University of New JerseyLary A. Robinson - Moffitt Cancer CenterBryan P. Schneider - Indiana University HealthEric A. Singer - The Ohio State UniversityAhmad A. Tarhini - Moffitt Cancer CenterGabriel Tinoco - The Ohio State UniversityCornelia M. Ulrich - Huntsman Cancer InstituteYousef Zakharia - University of IowaDaniel Spakowicz - The Ohio State UniversityAik Choon Tan - Huntsman Cancer InstituteCarlos H. Chan - University of Iowa, Surgery
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.84(6_Supplement), pp.7615-7615
- DOI
- 10.1158/1538-7445.AM2024-7615
- ISSN
- 1538-7445
- eISSN
- 1538-7445
- Language
- English
- Date published
- 03/22/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Surgery; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984648354402771
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