Abstract 1023: Whole-genome methylation analysis using liquid biopsy for pancreatic cancer diagnosis
Authors: Ito Tomoaki , Iwasawa Takuya , Takeda Satoshi , Okamoto Chikako , Motohashi Tomoko , Ueda Shuhei , Kato Hisaki , Yamamoto Riku , Koizumi Akihiro , Murai Yuta , Nihei Kosaku , Itakura Moe , Akima Ryunosuke , Sakurada Mutsumi , Tanaka Kenichiro , Kushida Tomoyuki , Sato Koichi 
Published: March 2024

Abstract
Objective: Pancreatic cancer is one of the highly malignant tumors. Its diagnosis requires invasive ultrasound endoscopic biopsy or endoscopic retrograde cholangiopancreatography (ERCP). However, these methods are limited by false-positive results and complications. Liquid biopsy, which uses blood to detect KRAS mutations in cancer, can be used to overcome these hurdles. However, only about 30% of cases can be detected as a diagnostic marker by KRAS mutations using plasma from patients with stage I-II pancreatic cancer, and its clinical application remains a challenge. Therefore, in this study, we focused on diagnosing pancreatic cancer using methylated DNA in plasma cell-free DNA (cfDNA) obtained from pancreatic cancer and non-cancer patients.
Subjects: Plasma was collected before the start of the treatment from six patients diagnosed with pancreatic cancer from 2019 to 2023 at our hospital, and six non-cancer patients simultaneously.
Methods: Whole-genome bisulfite sequencing (WGBS) using next-generation sequencing (NGS) was performed using the cfDNA obtained from the plasma of pancreatic cancer and non-cancer patients.
Results: The cfDNA fragments obtained by WGBS revealed that promoter regions were mostly deleted, and no difference was observed between cancer and non-cancer patients. The methylation rate of cfDNA fragments by WGBS differed between cancer and non-cancer patients, with multiple methylation sites (&gt;100 sites) in intergenic regions.
Discussion: Although attempts have been made to diagnose cancer using genetic mutations and liquid biopsy, only a few studies are available on using methylation markers in the plasma cfDNA of pancreatic cancer patients, and the effectiveness of this method remains unclear. In the present study, we found that promoter regions were deleted by WGBS, and several distinct hypermethylated regions were present in the intergenic region between pancreatic cancer and non-cancer samples, suggesting the presence of certain markers that can distinguish between pancreatic cancer and non-cancer patients.
Conclusion: This small number of cases suggests that hypermethylation of the intergenic regions could be helpful in the diagnosis of pancreatic cancer. We will need more cases in the future to verify the usefulness of hypermethylation of intergenic regions in the diagnosis of pancreatic cancer.
Citation Format: Tomoaki Ito, Takuya Iwasawa, Satoshi Takeda, Chikako Okamoto, Tomoko Motohashi, Shuhei Ueda, Hisaki Kato, Riku Yamamoto, Akihiro Koizumi, Yuta Murai, Kosaku Nihei, Moe Itakura, Ryunosuke Akima, Mutsumi Sakurada, Kenichiro Tanaka, Tomoyuki Kushida, Koichi Sato. Whole-genome methylation analysis using liquid biopsy for pancreatic cancer diagnosis [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 1023.