Abstract
Abstract Background: Pancreatic cancer is the most dreadful malignant tumor and expected becoming the second cause of death in 2030. Despites of vigorous studies, there were no definitive prognostic biomoleculars marker for pancreatic cancer. Herein, we already established primary pancreatic cancer cell lines from the real patients of pancreatic cancer, using conditionally reprogrammed cell culture (CRC). We tried to find novel prognostic biomarkers with multi-omics analysis of our primary pancreatic cancer cell lines. Methods: In this study, we selected pancreatic cancer prognostic markers using established CRCs and FFPE samples and validated the molecular mechanism of LXN. As the first step, we performed both transcriptome and proteome analysis using RNA sequencing and liquid chromatography-tandem mass spectrometry (LC/MS-MS) with 6 primary pancreatic cancer cell lines established by CRC. After analysis, we mined several candidate markers of prognosis including latexin (LXN) and sialic acid acetylesterease (SIAE). And we validated these markers clinicopathologically using immunohistochemical (IHC) staining of 136 tissues from a different set of pancreatic cancer patients. And we confirmed the knock-down effect of LXN using siLXN in pancreatic cancer cells. Results: We selected 2 highly prognostic markers with LXN and SIAE after transcriptome and proteome analysis. In these genes, high LXN expression group showed longer median overall survival (OS) than low expression group, respectively (14.8 vs. 10.4 months, P-value=0.28), respectively. For the evaluation of IHC, we established 3D organoid model using CRCs and confirmed the correlation between mRNA expression and protein expression with western blotting and IHC. The expression of Akt/mTOR was decreased after siLXN treatment compared to control groups. In order to validation as a prognostic marker, we stained formalin-fixed, paraffin-embedded (FFPE) slide from 136 pancreatic cancer patients. After IHC analysis, LXN high group (H-score > 12) showed significantly longer OS than low LXN group (52 vs. 28 months, P-value = 0.043). Conclusion: In this study, we found LXN as a prognostic marker with inhibition of proliferation utilizing patient-derived cancer model and FFPE samples. Citation Format: Chan Hee Park, Hee Seung Lee, Jin Su Kim, Yoo Keung Tae, Jin Young Lee, Seungmin Bang. Functional evaluation of pancreatic cancer prognostic marker, LXN, utilizing multiomics analysis based on patient-derived cancer model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3955.
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