Use of distinct molecular signatures of appendiceal cancer subtypes to assess biomarker development.

• DOI: 10.1200/jco.2023.41.4_suppl.189
• Publication Date: 2023-01-24T21:05:07Z
• Authors: Wan Ying Tan; Melissa Tian; Nensi Ruzgar; Astrid Hengartner; Bethsebie Sailo; Olivia Ang-Olson; Airol Ubas; Nithyla John; Vesal Yaghoobi; Haoyu Tang; Anup Sharma; ILKe Nalbantoglu; Nita Ahuja
• Keywords: Pseudomyxoma Peritonei

189 Background: Appendiceal Neoplasms are diverse entities which have a variety of clinical presentations, histologic subtypes, biologic behavior, and patient outcomes. Advanced disease at initial diagnosis is not uncommon therapeutic options limited. This study aims to identify potential targets develop epigenetics-based therapeutics/biomarkers. Methods: Archival (FFPE) specimens were collected from 25 patients with histologically confirmed subtyped appendiceal neoplasia 16 age-matched non-neoplastic controls. Four neoplastic processes identified: Low grade neoplasm (LAMN), pseudomyxoma peritonei (intra-peritoneal spread LAMN), conventional-type adenocarcinoma goblet cell adenocarcinoma. Gene expression profiling was performed using the HTG EdgeSeq Oncology Biomarker panel. Differentially expressed genes (DEGs) selected cut-off threshold FDR<0.05 analyzed Qlucore Explorer functional analyses via Ingenuity Pathway Analysis (IPA). Results: (20%), low-grade mucinous (24%), (32%). Unsupervised hierarchical clustering identified 498 DEGs (424 up, 74 down) between all cancer versus controls that showed enrichment in B-cell inflammatory signaling, senescence, cycle regulation, PI3K/AKT checkpoint control pathways, sets relating NANOG stem pluripotency (all p0.001). G1/S checkpoint, apoptosis, ATM, PTEN signaling downregulated (p0.001). TP53, E2F1, IL6, IFNG, TNF, HGF (p0.001) regulated overlapping genes. Four-subgroups comparison found 67 involved T-helper differentiation, immune-mediated T-cell fatigue, PD1/PDL1 be dysregulated FGF2, POU5F1, MYC upstream regulators. Conclusions: In this study, gene expressions cancers related proliferation death mechanisms, trend towards overexpression pathways. It postulated these pathways hypermethylated. More research being undertaken on biomarkers for prognosis. Given PI’s decades experience biomarker research, we aim "single blood test" expand bedside monitoring alternatives align National Cancer Moonshot Initiative discover early, when likelihood cure highest.