https://ir.ymlib.yonsei.ac.kr/handle/22282913/168904 2026-04-20T10:35:49Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211254 Title: Development and Performance Validation of a Comprehensive Liquid Biopsy Genotyping Panel for Pan-cancer Analysis Authors: Lim, Seoyoung; Lee, Kwang Seob; Won, Dongju; Seo, Sung Hyun; Lee, Seung-Tae; Choi, Jong Rak; Seo, Jieun; Shin, Saeam; 이광섭 Abstract: Background: Precision oncology is advancing, increasing the demand for comprehensive, non-invasive genomic profilingtools. Liquid biopsy using circulatingtumor DNA (ctDNA) enables real-time molecular profiling, treatment monitoring, and early detection of resistance variants. We developed the PAN100 panel (Dxome), a hybridization capture panel targeting 101 genes, as a pan-cancer genotyping assay to detect clinically actionable variants across various cancer types. This study presents the first comprehensive validation of the PAN100 panel including both analytical and clinical performance across eight cancer types using reference materials and matched tissue samples. Methods: For analytical validation, we assessed accuracy, limit of detection (LoD), and precision using Seraseq ctDNA v2 Reference Materials (SeraCare, Milford, MA, USA). Clinical validation was performed using plasma samples from 27 patients with eight types of cancer and 17 matched tumor samples. Positive percent agreement (PPA) between ctDNA and tissue next-generation sequencing (NGS) results was assessed using TruSight Oncology 500 and TruSight Tumor 170 assays. The limit of blank (LoB) was evaluated in 34 healthy individuals. Results: The PAN100 panel demonstrated high precision and linearity (LoD, 0.3%; 95.0% confidence interval, 0.29-0.35) variant allele frequency. The PPA between ctDNA and tissue NGS was 73.1% for single-nucleotide variants, 80.0% for insertions/deletions, and 74.2% overall. The LoB was 0.00001%. Conclusions: The PAN100 panel is a robust tool for detecting clinically significant variants with high concordance with tissue NGS. Its sensitivity for low-frequency variants enables real-time treatment adaptation, supporting precision oncology. Its comprehensive design is particularly valuable for challenging diagnoses and clonal evolution monitoring. 2026-03-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211474 Title: Nutrient Availability Dictates Cancer Metabolism-Based Therapeutic Responses to Nononcology Drugs Authors: Pyun, Woo Yang; Park, Jae Hyung; Roh, Jae Won; Jeon, Dongkyu; Kim, Jongwan; Paik, Ji Eun; Cho, Seok Chan; Park, So Yeon; Lim, Hocheol; Kim, Hyungwoo; Jang, Young Jin; Lee, Jaehoon; Byun, Jong Hwa; Son, Dong Woo; Kim, Soo-Youl; Guan, Kun-Liang; Lee, Won Dong; Gee, Heon Yung; Lee, Han-Woong; No, Kyoung Tai; Choi, Yu Suk; Hashimoto, Tadayoshi; Yoshino, Takayuki; Jeong, Han-Sol; Namkung, Wan; Nam, Joo Hyun; Park, Hyun Woo; 노재원 Abstract: Metabolic dysregulation is a major hallmark of cancer, making interventions that modify tumor nutrient availability attractive adjuvants for improving clinical outcomes for patients with cancer. Clarifying how the nutritional status of individual patients affects the metabolic vulnerability of tumors to drugs is needed to inform personalized treatment guidelines. Working toward the goal of oncometabolic precision medicine, we developed the cancer metabolism-based synthetic lethality platform (CM-SLP), a high-throughput screening platform that explores the metabolic vulnerability of cancer cells to nononcology drugs induced by altered nutrient availability and predicts potential synthetic lethal interactions with nutrient conditions. Promising CM-SLP candidates included propafenone and biguanides as representative nononcology drugs that cooperatively enhanced cytotoxicity via dysregulated metabolic pathways. Furthermore, the mTOR and Hippo pathways mediated the response to combined propafenone/hypoglycemia or biguanides/hypoglycemia treatments, respectively, and mTOR or TEAD inhibitors circumvented the need for dietary interventions to enhance cancer cell death. Together, these results indicate that CM-SLP represents a promising approach for integrating metabolic profiling into precision oncology, offering therapeutic avenues tailored to individual patient needs.Significance: A high-throughput screening approach investigating drug vulnerabilities dependent on nutrient status supports repurposing FDA-approved compounds as metabolically informed therapies for next-generation oncometabolic precision medicine. 2026-03-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211483 Title: A 62-aa core of the cochlin LCCL domain induces macrophage M1 polarization in vitro Authors: Kim, Hyoyeol; Bae, Seong Hoon; Jang, Seung Hyun; Yoon, Soljee; Kim, Kyeonghwan; Jang, Seung Hyeon; Gee, Heon Yung; Kim, Youngsoo; Jung, Jinsei; 장승현 Abstract: BackgroundCochlin, encoded by the COCH gene, mediates innate immunity against bacterial infections by segregating pathogens and recruiting immune cells through its N-terminal LCCL domain. This domain is cleaved and secreted to attract macrophages and neutrophils, but its core motif has remained unclear.MethodsWe designed and synthesized a shortened core peptide of the LCCL domain (cLCCL; 62 amino acids) preserving the conserved structural motif. Structural stability was predicted by in silico modeling. The immunomodulatory effects of LCCL and cLCCL were evaluated in RAW264.7 macrophage cells using bulk RNA sequencing, quantitative PCR, Western blotting, flow cytometry, and immunocytochemistry.ResultsRNA sequencing in RAW264.7 cells showed that both LCCL and synthetic cLCCL peptides induced M1 polarization, with upregulation of TICAM2, CD40, and CD86. Flow cytometry demonstrated a significant increase in CD40(+)/CD86(+) M1-polarized macrophages following LCCL or cLCCL treatment, with comparable effects between the full-length and core peptides.ConclusionThe identified cLCCL appears to promote pro-inflammatory macrophage polarization, activate pro-inflammatory innate immune pathways, and warrants further evaluation in mechanistic and in vivo studies. 2026-03-01T00:00:00Z https://ir.ymlib.yonsei.ac.kr/handle/22282913/211540 Title: HAP1 interaction with KCNQ4 attenuates channel surface expression and function Authors: Kim, Jung Ah; Oh, Kyung Seok; Roh, Jae Won; Koh, Young Ik; Lin, Haiyue; Jung, Jinsei; Gee, Heon Yung Abstract: The voltage-gated channel subfamily Q member 4 (KCNQ4), a K+ channel, is one of the most frequently mutated genes in autosomal dominant nonsyndromic hearing loss. KCNQ4, which contains 6 transmembrane domains and a long cytoplasmic C-terminal tail, plays a crucial role in K+ recycling in the inner ear. Although KCNQ4 binds to various interactors, specific binding sites of the interactors remain elusive, and the biological significance of these interactions remains unknown. Therefore, this study aimed to discover a novel interactor of KCNQ4 and delineate its functional role in KCNQ4 regulation. We discovered a novel interactor of KCNQ4, huntingtin-associated protein 1 (HAP1), in addition to calmodulin, which interacts with the C-terminus of KCNQ4 using a yeast 2-hybrid assay. This interaction requires the B-segment of KCNQ4 as demonstrated by protein domain analysis. A thorough investigation of the biochemical and physiological consequences of this association revealed that HAP1 overexpression reduced surface expression and attenuated the potassium current mediated by KCNQ4. This suggests that HAP1 acts as a negative regulator of KCNQ4, potentially through the disruption of normal endocytic trafficking. These findings enhance the understanding of KCNQ4 regulation at the molecular level and highlight the potential of the HAP1-KCNQ4 axis as a target for interventions aimed at maintaining channel surface stability. (c) 2026 The Author(s). Published by Elsevier Inc. on behalf of Korean Society for Molecular and Cellular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2026-03-01T00:00:00Z