Abstract 2523: Predictive biomarkers for neoadjuvant FLOT4 chemotherapy response in gastroesophageal cancer: Results of multi-omics approach

Abstract

Abstract Background: The FLOT4 chemotherapy regimen is a standard preoperative treatment for gastroesophageal junction (GEJ) and gastric cancer (GC), yet the response to this treatment is variable. Identification of predictive biomarkers is crucial for optimizing therapeutic strategies. This study aims to identify predictive biomarkers for FLOT4 treatment efficacy using a multi-omics approach. Methods: We conducted a preliminary differential gene expression analysis in diagnostic tissue pre-treatment and surgical resection post-treatment in six patients (two GEJ and four GC) who all exhibited a partial pathological response (G2) to neoadjuvant FLOT4 chemotherapy. Utilizing DESeq2 for differential gene expression and David pathway analysis for functional insights, we have begun to unravel the complex molecular response to treatment. Upcoming assays include blood gDNA and tumor tissue whole exome sequencing (WES), comprehensive methylation profiling, miRNA characterization, and proteomics via LC-MSMS. Results: Our preliminary data suggest alterations in gene expression associated with cell adhesion, extracellular matrix interaction, and immune response pathways. Three common genes (CXCL2, CXCL3, CXCL1) were identified among upregulated pathways in GEJ patients, while one common gene (IL1A) was observed in GC patients. These findings suggest a complex network of biological processes influenced by FLOT4. In-depth results, including whole-exome sequencing, methylation patterns, and miRNA profiles, will be completed and presented at the conference. Conclusion: These initial findings propose that changes in gene expression related to cellular architecture and immune response are indicative of a partial response to FLOT4 in both GEJ and GC patients. The identified genes and pathways may serve as potential biomarkers for predicting treatment outcomes. Future Directions: By the time of the conference, we anticipate including a more extensive patient cohort with complete response or no response to FLOT4, and comparative analyses with a FOLFOX treatment group. The integration of forthcoming WES, methylation, miRNA, and proteomics data will provide a more comprehensive molecular predictive model. Keywords: FLOT4 chemotherapy, gastroesophageal junction cancer, gastric cancer, predictive biomarkers, differential gene expression. Citation Format: Amira Al-Fahdi, Shoaib Al Zadjali, Ibrahim Al Haddabi, Anoopa Pullanhi, Muna Al Jabri, Aida Al Yayahee, Nada Al Shuaili, Nahad Al Mahrouqi, Mansour Al Moundhri. Predictive biomarkers for neoadjuvant FLOT4 chemotherapy response in gastroesophageal cancer: Results of multi-omics approach [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 2523.