Abstract B068: Novel Liquid Biopsy Gene Panel for Potential Early Diagnosis of PDAC with High Accuracy

Abstract Introduction: Pancreatic Ductal Adenocarcinoma (PDAC) ranks as the third most lethal cancer in the United States. The American Cancer Society estimates 67,440 people will be diagnosed in 2025 while expecting 51,980 deaths (∼77% mortality). The high number of deaths highlights the importance of developing early detection methods. PDAC progresses without noticeable symptoms which results in a delayed often associated with metastatic and highly aggressive disease. The systemic molecular signals present in whole blood provide a minimally invasive method for biomarker development to detect PDAC at an early stage. Methods: The present research involved prospective blood sample collection from four patient groups consisting of Pancreatic Cysts (n=16), Intraductal Papillary Mucinous Neoplasm (IPMN; n=14), PDAC (n=43) and healthy controls (n=36). Total RNA was extracted using TRIzol and RNeasy kits followed RNA QC by bioanalyzer. RNA-seq was performed on NovaSeq 6000 and the data analyzed using Partek Flow software on HPC server. QS7 instruments were used for real-time PCR with TaqMan assays. Results: RNA-seq data analysis revealed 1,703 genes with statistically significant differential expressions between PDAC and controls (FC >1; p<0.05). For discovery of biomarkers, we also used publically available RNA-seq data mining along with literature mining and identified 36 genes for further assessment. The 36 genes underwent quantitative PCR (qPCR) analysis using PDAC, IPMN, Cyst and Control whole blood samples. This qPCR data was used to develop a machine learning (ML) algorithm, based on this biomarker panel. The ML analysis revealed 21 genes that effectively distinguished PDAC from control samples. The biomarker panel-based algorithm achieved high diagnostic accuracy with different comparison groups as: PDAC vs. Controls (AUC = 1.00), IPMN vs. Controls (AUC = 1.00), PDAC + IPMN vs. Controls (AUC = 1.00) and PDAC + IPMN vs. Controls + Cysts (AUC = 0.913). Conclusions: This data presents with a novel PDAC-specific 21-gene panel in whole blood, which demonstrates 100% sensitivity and specificity for differentiating PDAC from controls and 100% for PDAC versus benign cysts. A larger clinical study is needed to verify this approach, the data demonstrates the potential for early diagnosis of PDAC using mRNAs as liquid biopsy tool from whole blood samples. Citation Format: Srinivas V. Koduru, Mark Kidd, ignat Drozdov, Abdel Halim. Novel Liquid Biopsy Gene Panel for Potential Early Diagnosis of PDAC with High Accuracy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B068.