Abstract B063: Immune cell expression-based multi-biomarker blood panel for early detection of pancreatic ductal adenocarcinoma

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose at an early stage due to the limited sensitivity and specificity of current biomarkers. Most patients are diagnosed at advanced stages, limiting treatment options. The immune surveillance hypothesis highlights the critical role of the immune system in PDAC development and progression. To address the need for improved early detection, we developed and validated a blood-based multi-biomarker panel—including CA19-9—that quantifies gene expression in peripheral blood immune cells, enabling non-invasive and more accurate diagnosis in patients with radiologically suspicious pancreatic lesions. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy controls and patients with various diseases, including PDAC, in a prospective case-control study. RNA sequencing was performed to identify PDAC-associated immune cell gene expression markers. Four markers (IL-7R, PLD4, ID3, S100A11) were selected based on their PDAC-specific expression profiles. Their expression in PBMCs was measured by real-time PCR, and serum CA19-9 was quantified by ELISA. A biomarker panel formula was developed using a development cohort (n=272; PDAC=50, non-PDAC=222) and validated in an independent cohort (n=310; PDAC=170, non-PDAC=140) of patients with CT-suspected pancreatic lesions. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) were calculated and compared to CA19-9 and CT imaging. Results: In the development cohort (n=272), the five-marker panel consisting of PLD4, IL-7R, ID3, S100A11, and CA19-9 demonstrated a sensitivity of 96.0%, specificity of 76.1%, and accuracy of 79.8%, outperforming CA19-9 alone. In the validation cohort (n=310), the panel achieved a sensitivity of 90.0%, specificity of 70.0%, accuracy of 81.0%, and an area under the curve (AUC) of 0.800, showing a superior balance between sensitivity and specificity compared to CA19-9 and CT imaging. Stage-specific analysis in the validation set revealed sensitivities of 86.7% for stage I, 91.2% for stage II, 90.9% for stage III, and 89.4% for stage IV, indicating robust diagnostic performance across all disease stages. Distinct immune cell expression patterns were observed: PLD4 expression was reduced in myeloid cells, IL-7R was increased in CD4+ T cells, ID3 was upregulated in B cells, macrophages, and M-MDSCs, and S100A11 was elevated in MDSCs. These characteristic immune cell changes are specific to PDAC and serve to distinguish it from other solid tumors. Conclusions: This five-marker blood panel enables sensitive, specific, and non-invasive detection of PDAC, outperforming conventional biomarkers and CT imaging. By leveraging unique immune cell expression signatures, the panel provides robust diagnostic performance across all disease stages and supports its utility for early diagnosis and improved management of patients with radiologically suspicious pancreatic lesions. Citation Format: SO YOUNG KIM, Sung Ill Jang, Jae Hee cho, See Young Lee, Eun-Ju Chang, Jong Kyoung KIM, In Young Hong, JIO Choi, Somi KIm, Nahyeon Park, Dong Ki Lee, Hyung Keun Lee. Immune cell expression-based multi-biomarker blood panel for early detection of pancreatic ductal adenocarcinoma [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 B063.