Abstract 1491: Investigation of differentially expressed miRNAs in patients with gastric adenocarcinoma

Abstract

Gastric cancer (GC) is one of the most common cancers and one of the leading causes of cancer related death worldwide. Although the treatment of GC patients has improved during the last decades, thanks to advancements in surgery, radiotherapy and chemotherapy, the long-term survival rates of patients with GC remains around 20%. In addition, late diagnosis usually occurs due to the absence of symptoms or the presence of non-specific symptoms in early stages of the disease. Thus, the continuous study of new strategies for early diagnosis and identification of novel therapeutic approaches is of great interest, to reduce the need for mutilating surgeries and morbid adjuvant therapies. Next-generation sequencing technologies unveiled new roles and functions of RNAs, particularly, non-coding RNAs. Among the most studied molecules, microRNAs (miRNAs) have been reported to play important roles in different physiological and pathological processes, including cancer. Therefore, the goals of this project are (1) to determine the miRNA profile of patients with GC using tumor tissue samples using next-generation sequencing; and (2) to validate the expression profile of differentially expressed (DE) miRNAs in serum from patients with GC. To identify DE microRNAs between GC tissues and gastric tissues from individuals without cancer, 24 samples (17 cancer and 7 controls) were sequenced using the Ion Torrent PGM (Thermo Fisher Scientific) sequencing equipment. Preliminary results indicate that there are 54 DE miRNAs among the 269 known human miRNAs identified, where 44 were upregulated, while 10 were downregulated in samples from GC patients when compared to samples from individuals without cancer. As expected, Over-Representation Analysis (ORA) revealed that the disease most frequently associated with these DE miRNAs is the digestive system neoplasm. Moreover, Gene Set Enrichment Analysis (GSEA) showed that neoplasm metastasis is the phenotype most associated with this subset of DE miRNAs, indicating that these miRNAs possibly contribute to cell invasion and migration in gastric tumors. To confirm these findings, further experiments are now being performed, such as validation of the DE miRNAs by qRT-PCR in tissue and serum of GC samples, as well as functional studies. Thereby, the identification of a circulating signature of miRNAs will allow a better understanding of physiopathology of gastric carcinogenesis and the identification of possible biomarkers, which may help in early diagnosis, prognosis, and development of novel anticancer therapies.Funding: MACS, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grant # 2016/25562-0; MACS, Conselho Nacional de Pesquisa (CNPq) grant # 2018/301127-2; MACS, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 23038051640/2009-01; BTRK, Postdoctoral Fellowship, FAPESP 2019/20592-6; CAP, CAPES Doctoral Fellowship 88882.430351/2019-01. Citation Format: Bruno Takao Real Karia, Camila Albuquerque Pinto, Leonardo Caires, Yeda Beatriz Louredo dos Santos, Fernanda Wisnieski, Carolina Gigek, Marilia de Arruda Cardoso Smith. Investigation of differentially expressed miRNAs in patients with gastric adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1491.