Annual Report 2024

Department of Proteomics

Shungo Adachi, Mari Masuda, Sumiko Ohashi, Hideo Kusano, Kumiko Nishimura, Masae Homoto, Tatsuki Yokoseki, Shuhei Mitsutomi, Jion Kozawa

Introduction

 Our division is dedicated to advancing cancer research and clinical translation through state-of-the-art mass-spectrometry-based proteomics. By integrating high-precision analytical technologies with clinical needs, we aim to deepen biological understanding while directly contributing to precision oncology. Following the establishment of core infrastructure in FY2023, FY2024 was marked by technical maturation, full-scale operational deployment, and strengthened collaboration with clinical departments.

The Team and What We Do

 The team currently consists of nine specialists with expertise spanning sample preparation, automation, mass spectrometry, computational analysis, and translational research. This multidisciplinary structure enables an integrated workflow from clinical specimen processing to high-dimensional data interpretation, supporting diverse research initiatives and advancing clinical proteomics capacity within the institution.

Research Activities

 We optimized instrument performance and automated sample-processing workflows, establishing a high-throughput proteomics platform capable of analyzing approximately 50 samples per day. Key accomplishments include:

• Development of precision protocols for frozen tissue, FFPE samples, plasma, cerebrospinal fluid, and immunoprecipitated materials
• Transition to magnetic-bead-based processing and establishment of a 96-well automated workflow for highly reproducible analyses
• Implementation of an integrated data-analysis framework covering quality control, statistical evaluation, pathway analysis, and visualization

 These advances enabled high-efficiency, high-accuracy analysis of heterogeneous clinical specimens and supported ten research and clinical projects across the Research Institute and Central Hospital, contributing to biomarker discovery and improved understanding of disease mechanisms.

Education

 We actively contributed to academic dissemination and human resource development. Activities included knowledge sharing through seminars and collaborative research, as well as mentoring young researchers and clinicians in advanced proteomics technologies and data interpretation, fostering the next generation of leaders in precision oncology and quantitative biology.

Future Prospects

 From FY2025 onward, we will further accelerate the integration of clinical proteomics and precision oncology through:

• Large-scale analysis of biobank and prospective clinical samples linked to clinical information
• Standardization of analytical workflows and quality benchmarks for clinical implementation
• Emphasis on liquid-biopsy proteomics (blood and cerebrospinal fluid) for early diagnosis, therapeutic monitoring, and relapse prediction
• Continued expansion of automation and AI-enhanced analytical pipelines to maximize reproducibility and scalability

 Through these initiatives, our division will contribute to the establishment of an advanced medical platform for cancer control and to the realization of next-generation precision medicine at the National Cancer Center.

List of papers published in 2024

Journal

1. Tsuge A, Watanabe S, Kawazoe A, Togashi Y, Itahashi K, Masuda M, Sai A, Takei S, Muraoka H, Ohkubo S, Sugiyama D, Yan Y, Fukuoka S, Doi T, Shitara K, Koyama S, Nishikawa H. The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment. Cancer immunology research, 13:273-285, 2025

2. Sasaki T, Iwaya T, Yaegashi M, Idogawa M, Hiraki H, Abe M, Koizumi Y, Sasaki N, Yashima-Abo A, Fujisawa R, Endo F, Tange S, Otsuka K, Sasaki A, Masuda M, Fujita M, Nakagawa H, Takahashi F, Sasaki Y, Tokino T, Nishizuka SS. Impact of Sensitive Circulating Tumor DNA Monitoring on CT Scan Intervals During Postoperative Colorectal Cancer Surveillance. Annals of surgery open : perspectives of surgical history, education, and clinical approaches, 6:e549, 2025

3. Masuda M, Nakagawa R, Kondo T. Harnessing the potential of reverse-phase protein array technology: Advancing precision oncology strategies. Cancer science, 115:1378-1387, 2024

4. Maru Y, Kohno M, Suzuka K, Odaka A, Masuda M, Araki A, Itami M, Tanaka N, Hippo Y. Establishment and characterization of multiple patient-derived organoids from a case of advanced endometrial cancer. Human cell, 37:840-853, 2024

5. Mochizuki M, Shibuya-Takahashi R, Kanno SI, Adachi S, Fujimori H, Nakazato A, Fujii K, Morita S, Saijoh S, Yamazaki T, Imai T, Asada Y, Yamaguchi K, Yasuda J, Shindo N, Sugamura K, Tamai K. CD271 mRNA/hnRNPA2B1 complex promotes proliferation and stemness in oral and head and neck squamous cell carcinoma. Cancer science, 115:2346-2359, 2024

6. Udagawa D, Nagata S, Yagi H, Nishi K, Morisaku T, Adachi S, Nakano Y, Tanaka M, Hori S, Hasegawa Y, Abe Y, Kitago M, Kitagawa Y. A Novel Approach to Orthotopic Hepatocyte Transplantation Engineered With Liver Hydrogel for Fibrotic Livers, Enhancing Cell-Cell Interaction and Angiogenesis. Cell transplantation, 33:9.6369E+15, 2024

7. Kato A, Iwasaki R, Takeshima K, Maruzuru Y, Koyanagi N, Natsume T, Kusano H, Adachi S, Kawano S, Kawaguchi Y. Identification of a novel neurovirulence factor encoded by the cryptic orphan gene UL31.6 of herpes simplex virus 1. Journal of virology, 98:e0074724, 2024

8. Kaneko S, Takasawa K, Asada K, Shiraishi K, Ikawa N, Machino H, Shinkai N, Matsuda M, Masuda M, Adachi S, Takahashi S, Kobayashi K, Kouno N, Bolatkan A, Komatsu M, Yamada M, Miyake M, Watanabe H, Tateishi A, Mizuno T, Okubo Y, Mukai M, Yoshida T, Yoshida Y, Horinouchi H, Watanabe SI, Ohe Y, Yatabe Y, Saloura V, Kohno T, Hamamoto R. Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations. Molecular cancer, 23:126, 2024

9. Tokuoka SM, Hamano F, Kobayashi A, Adachi S, Andou T, Natsume T, Oda Y. Plasma proteomics and lipidomics facilitate elucidation of the link between Alzheimer's disease development and vessel wall fragility. Scientific reports, 14:19901, 2024

10. Yagi H, Yamada R, Saito T, Honda R, Nakano R, Inutsuka K, Tateo S, Kusano H, Nishimura K, Yanaka S, Tojima T, Nakano A, Furukawa JI, Yagi-Utsumi M, Adachi S, Kato K. Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway. iScience, 27:111457, 2024