서울대학교 생물정보학 협동과정 주최로 세미나를 아래와 같이 열고자 하오니 많은 참여 바랍니다.

세미나는 대면 강의로 예정되어 있으며 강의에 참여하고자 하시는 분께서는 아래 일시와 장소를 참고하여 주시길 바랍니다.

일시: 2023년 9월 19일 화요일 오전 11시

연사: 박대찬 교수님 (아주대학교)

장소: 500동 L304호
(500동건물에서 503동 건물 방향 엘리베이터 이용)

Title: Comprehensive Genomic Studies on Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer, is characterized by aggressive tumor behavior and poor prognosis. PDAC is one of the cancers with the lowest tumor cellularity, a proportion of tumor cells in a tissue. Large-scale genomic studies showed that the median cellularity of PDACs was only 26 % comparing to that of all cancers was 81.1%. This low tumor cellularity results in the heterogeneity and complexity of the stromal environment consisting of various non-cancer cells.

To interrogate the complex environment of PDAC, we analyzed mRNA sequencing data of 196 PDAC tissue samples and estimated cell-type abundances from each bulk RNA data based on a single-cell reference profile using digital cytometry. Samples of the aberrantly differentiated endocrine exocrine (ADEX) subtype had a vast majority number of acinar cells than others. Interestingly, the stromal environment and the molecular subtypes were significantly altered in the patient-derived xenograft (PDX), where the environment stimulates selection and evolution of tumor and stromal cells.

Next, we aimed to maximize the use of multi-omics data and readily available clinical factors through focusing on novel 8 marker genes and the KRAS codon 12 mutation for clinical application. We obtained RNA sequencing, whole exome sequencing, and KRAS targeted sequencing simultaneously from 193 PDAC specimen. KRAS mutant dosage had comparable performance with clinical variables for survival prediction, and high levels of KRAS mutant dosages accelerated cell cycle resulting in poor clinical outcomes. We also established a prognostic scoring system by integrating mutant dosage with clinical factors. The high prediction power of the scoring system for survival outcomes and timing of recurrence demonstrated its integrity, feasibility, and efficiency with clinical significance.