Abstract A41: Cancer-associated fibroblast (CAF) specific biomarkers in pancreatic ductal adenocarcinoma (PDAC): Transcriptomic and molecular insight

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of malignancy-related death with poor prognosis. The late diagnosis due to nonspecific symptoms, highly aggressive nature, intrinsic resistance to chemotherapeutic, and the lack of effective therapeutic are the main causes of poor prognosis in PDAC. This cancer type comprises up to 90% cellular component of desmoplastic stroma that holds a major role in drug resistance and malignancy. The complexity of the genome is another leading cause of molecular alteration in PDAC. Hence, the urge to find the prognosis marker for PDAC is extremely needed for the new therapeutic regimens. In this study we performed RNA-seq analysis from MSC in single and co-cultured conditions (in vitro), MSC and Xeno-MSC (in vivo), and patient-derived CAF. Read alignment and junction mapping was accomplished using HISAT2 and cufflinks respectively and followed by map reads using UCSC hg38 reference genome annotation. Data were expressed as fragments per kilobase of exon per million fragments mapped (FPKM). Three out of eight clusters on heatmap were selected based on their expression pattern across all the samples. Approximately 900 transcripts from selected clusters were classified into three major protein classes: transcription factors, kinases, and membrane proteins. Remarkably, several genes on selected clusters have been studied in CAF, giving proof of the fidelity of our data analysis. Prompted to get more specific CAF-related genes, we put more parameters such us: unexpressed in normal pancreatic, relatively low expression in pancreatic cancer, ≥2 folds increase of CAF mRNA expression to normal or pancreatic cancer, and have not studied in PDAC. We found 16 transmembrane protein-coding genes that are potentially involved in CAF remodeling. To gain a better understanding of tumor-CAF interaction from these candidate genes, immunostaining using paraffin sections from tumor-bearing mice model together with αSMA/IL6 and protein analysis was carried out. We sought the downstream pathways as well to discover novel regulatory networks and causal relationship between CAF and pancreatic cancer. Our study addresses the extent to which factor(s) can reset stromal alteration and elucidate the role of transmembrane protein during CAF reprogramming. Citation Format: Jayarani F. Putri, Yutaro Kumagai, Yoshihiro Miyazaki, T. Oda, Yasuyuki S. Kida. Cancer-associated fibroblast (CAF) specific biomarkers in pancreatic ductal adenocarcinoma (PDAC): Transcriptomic and molecular insight [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A41.