Abstract 195P
Background
Ferroptosis is a type of programmed cell death dependent on iron metabolism distinct from necrosis and apoptosis. In pancreatic ductal adenocarcinomas (PDAC), studies have noted that ferroptosis signatures are also associated with survival. However, no studies have attempted to find histological correlates which might suggest a ferroptosis process occurring.
Methods
PDACs from the Cancer Genome Atlas (TCGA) Pan-Cancer were used. Clinicopathological, DNA, histological slides, and mRNA expression data were extracted with the GDC Data Transfer Tool. A scree plot was generated to determine the optimal number of clustering groups based on ferroptosis molecular signatures. A K-means clustering approach was used in STATA. Groups of less than 5 patients were excluded. The ferroptosis-based clusters were correlated to clinical, histological, molecular, and survival parameters. Gene Set Enrichment Analysis (GSEA) was also performed by identified cluster. An adjusted α = 0.05 for statistical significance was used for all tests.
Results
175 PDAC cases were used from the TCGA. Optimal K-means clustering identified 4 distinct ferroptosis signature-based PDAC groups, which differed in gene expression. Group 1 (n=47) showed improved overall survival by log-rank analysis versus other 3 groups (p<0.05). There was no significant difference in age, sex distribution, tumor grade, necrosis or staging between Group 1 and other groups. Over-expressed genes in ferroptosis-based group 1 include MAP3K14, TNFAIP3, CYGb; underexpressed genes in Group 1 include EMC2, ZFAS1, CYP4F8. GSEA showed downregulation of EET, DHET and HETE synthesis, and upregulation of RNA metabolism, cell cycle and mitotic activity in Group 1 vs other 3 groups.
Conclusions
A comprehensive multimodal approach to ferroptosis expression signatures highlights a clinical impact on overall survival. However, after post-hoc analysis by two pathologists, no histological marker was identified to be significantly associated with ferroptosis signatures. Genes involved in group 1 modulate nF-κB signaling, target lipid peroxidation, and inhibit GPX4 function. Further ancillary testing of ferroptosis pathway in PDACs is warranted.
Editorial acknowledgement
Legal entity responsible for the study
Vincent Quoc-Huy Trinh.
Funding
Fonds de recherche Santé Québec.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
183P - Final analysis of phase II clinical study evaluating the safety and effectiveness of neoadjuvant S-1 + oxaliplatin combination therapy for older patients with locally advanced gastric cancer
Presenter: Eiji Oki
Session: Poster Display
Resources:
Abstract
184P - Neutropenia as a predictive and prognostic factor in nanoliposomal-irinotecan/fluorouracil/leucovorin therapy for pancreatic cancer: Findings from the NAPOLEON-2 study (NN-2301)
Presenter: Yuki Sonoda
Session: Poster Display
Resources:
Abstract
185P - Disease etiology impact on outcomes of hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: A real-world, multicenter study
Presenter: Silvia Foti
Session: Poster Display
Resources:
Abstract
186P - Efficacy and safety of fruquintinib with nab-paclitaxel in advanced G/GEJ cancer after exposure to immune checkpoint inhibitors: A single-center prospective clinical trial
Presenter: Xiaoting Ma
Session: Poster Display
Resources:
Abstract
187P - Neoadjuvant cadonilimab (PD-1/CTLA-4 bispecific antibody) plus transhepatic arterial infusion chemotherapy (HAIC) for resectable multinodular CNLC Ib/IIa hepatocellular carcinoma (Car-Hero)
Presenter: Yongguang Wei
Session: Poster Display
Resources:
Abstract
188P - Impact of metformin, statin, aspirin and insulin on the prognosis of unresectable HCC patients receiving first-line lenvatinib or atezolizumab plus bevacizumab
Presenter: Margherita Rimini
Session: Poster Display
Resources:
Abstract
189P - Safety run-in results from LEAP-014: First-line lenvatinib (len) plus pembrolizumab (pembro) and chemotherapy (chemo) for metastatic esophageal squamous cell carcinoma (ESCC)
Presenter: Shun Yamamoto
Session: Poster Display
Resources:
Abstract
190P - Perioperative camrelizumab combined with chemotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: A single-arm, single-center, phase II clinical trial
Presenter: Jiaxing He
Session: Poster Display
Resources:
Abstract
191P - Predictive value of CXCR6 expression in gastric cancer survival and immune modulation
Presenter: Song-Hee han
Session: Poster Display
Resources:
Abstract
192P - Antiangiogenesis-related adverse events (ARAE) to predict efficacy in patients with advanced gastric cancer (AGC) treated with apatinib + chemotherapy: Results from two prospective studies
Presenter: Rongbo Lin
Session: Poster Display
Resources:
Abstract