Annual Report 2024
Division of Biomarker Discovery (Kashiwa Campus)
Shuichi Mitsunaga, Tomofumi Miura, Hidetaka Suzuki, Yuriko Sato, Michiko Hamamoto, Tomoko Inagaki, Reiko Nakamura
Introduction
Our research mission involves the elucidation of tumor-driven abnormal responses of normal tissues from the perspective of clinical symptoms and the development of ways to control them. We are investigating new treatments and biomarkers to facilitate the clinical benefits for patients, especially those with pancreatic cancer.
The Team and What We Do
Systemic inflammatory reactions, metabolic abnormalities, and anorexia are often observed in patients with pancreatic cancer. They are major symptoms of cancer cachexia. Our research has been sourced from patient samples, clinical data, and animal models reproducing cachexia, and has provided an understanding of its pathophysiology, which is useful for developing new treatments. In particular, we are focusing on creating a proof-of-concept (POC) to engage medical seeds in a clinical trial.
Research Activities
Our cachexia research using a cancer-bearing mouse model and clinical samples identified abnormal amino acid metabolism in the liver and provided a joint industry-academia patent of a biomarker for predicting cancer cachexia. A peripheral blood memory T cell fraction is a mirror of a favorable clinical course in chemotherapy for pancreatic cancer. A joint industry-academia patent has been obtained for a discovery that measures the peripheral blood memory T cell fractions for predicting the recalcitrance of anti-cancer treatment and the worsening of cachexia symptoms.
We are actively involved in clinical trial groups. We joined a randomized controlled trial conducted by the Cachexia Group of the Japanese Society of Supportive Care in Cancer to evaluate the effectiveness of nutritional and exercise therapy, which is considered standard care, and published a paper on the results of the clinical trial as the first author. We also served as the core facility for a biomarker study conducted by the JCOG Hepato-Biliary-Pancreatic Group to predict the effectiveness of postoperative adjuvant chemotherapy for biliary tract cancer. In this study, we identified an RNA signature related to 5FU-metabolizing enzymes for predicting the effectiveness of postoperative S-1 therapy, and published a paper on the results as a first author.
We are focusing on the development of biomarkers for cancer detection. Our "serum microRNA test chip for detecting pancreatic and biliary cancer," which combines bioinformatics technology to increase diagnostic sensitivity, has been designated as a pioneering in vitro diagnostic tool, and we have published a paper demonstrating its robustness and diagnostic performance which will contribute to its practical implementation. We have identified a CD276 protein fragment that is specifically detected in the urine of pancreatic cancer patients, and published a paper demonstrating its usefulness for pancreatic cancer detection.
Education
We supervise one graduate student and two university students.
Future Prospects
We evaluate the potential usefulness of pharmaceutical or diagnostic seeds in developing their POCs for an appropriate clinical trial with the perspective of cancer-host interaction, and work together to take the next step.
List of papers published in 2024
Journal
1. Gotoh R, Shimizu Y, Hayashi A, Isseki M, Miura T, Inoue A, Takano M, Masukawa K, Aoyama M, Morita T, Kizawa Y, Tsuneto S, Shima Y, Miyashita M. Associations Between Anticipatory Grief and Post-Bereavement Depression and Post-Loss Grief of Family Members of Dying Patients With Cancer in Palliative Care Units: A Cohort Study. The American journal of hospice & palliative care, 10499091241313299, 2025
2. Mitsunaga S, Ikeda M, Ueno M, Kobayashi S, Tsuda M, Miki I, Kuwahara T, Hara K, Takayama Y, Matsunaga Y, Hanada K, Shimizu A, Yoshida H, Nomoto T, Takahashi K, Iwamoto H, Iwama H, Hatano E, Nakata K, Nakamura M, Sudo H, Takizawa S, Ochiai A. Robust circulating microRNA signature for the diagnosis and early detection of pancreatobiliary cancer. BMC medicine, 23:23, 2025
3. Imamura S, Watanabe K, Inoue K, Taira T, Shibuki T, Satake T, Yamaguchi S, Sasaki M, Imaoka H, Mitsunaga S, Ikeda M. Side-by-side versus stent-in-stent technique for stent deployment during systemic chemotherapy in biliary tract cancer patients with malignant hilar biliary obstruction. DEN open, 5:e70075, 2025
4. Amano K, Okamura S, Miura T, Baracos VE, Mori N, Sakaguchi T, Uneno Y, Ishiki H, Hiratsuka Y, Yokomichi N, Hamano J, Baba M, Mori M, Morita T. Clinical Implications of the C-Reactive Protein-Albumin Ratio as a Prognostic Marker in Terminally Ill Patients with Cancer. Journal of palliative medicine, 28:592-600, 2025
5. Shimotsuura Y, Ishizuka K, Kawaguchi T, Umetsu K, Harada M, Inoue Y, Kubo E, Kosugi K, Igarashi T, Enomoto S, Taniyama H, Iwata T, Yamaguchi T, Matsumoto Y, Miura T. Effects of High-Resolution Natural Sound with Inaudible High-Frequency Components on Healing, Symptoms, and Sleep Satisfaction in Terminally Ill Cancer Patients. Palliative medicine reports, 6:53-60, 2025
6. Inoue K, Fukushi K, Yamaguchi S, Taira T, Shibuki T, Satake T, Watanabe K, Sasaki M, Imaoka H, Mitsunaga S, Ikeda M. Treatment outcomes of gemcitabine plus nab-paclitaxel in pancreatic cancer patients with malignant ascites. Pancreatology, 24:616-623, 2024
7. Shibuki T, Fukushi K, Inoue K, Taira T, Satake T, Watanabe K, Sasaki M, Imaoka H, Mitsunaga S, Ikeda M. Covered self-expandable metallic stent placement for tumor bleeding from duodenal invasion in patients with unresectable pancreatic cancer. DEN open, 4:e361, 2024
8. Okamura N, Kubo E, Ishida A, Noda S, Harada M, Ishizuka K, Inoue Y, Kosugi K, Miura T. Differences in discharge letter content: oncologists' vs. home care physicians' needs. Supportive care in cancer, 32:299, 2024
9. Habu T, Kumagai S, Bando H, Fujisawa T, Mishima S, Kotani D, Nakamura M, Hojo H, Sakashita S, Kinoshita T, Yano T, Mitsunaga S, Nishikawa H, Koyama S, Kojima T. Definitive chemoradiotherapy induces T-cell-inflamed tumor microenvironment in unresectable locally advanced esophageal squamous cell carcinoma. Journal of gastroenterology, 59:798-811, 2024
10. Mitsunaga S, Okumura N, Takei T, Takao T, Tsubouchi H, Nakata K, Nakamura M, Kitahata Y, Motobayashi H, Ikeda M, Nakazato M. Identification of a urinary CD276 fragment for detecting resectable pancreatic cancer using a C-terminal proteomics strategy. Scientific reports, 14:14207, 2024
11. Mitsunaga S, Ikeda M, Nomura S, Morizane C, Todaka A, Yamamoto N, Kamata K, Yanagibashi H, Mizuno N, Kawamoto Y, Gotoh K, Shirakawa H, Okano N, Nomura T, Tanaka K, Takahashi A, Yagi S, Ohta K, Takayama Y, Miwa H, Nagano H, Kojima Y, Hisano T, Tahara M, Sakuma Y, Arai H, Nakamura I, Katayama H, Konishi M, Ueno M. 5-Fluorouracil metabolic pathway genes predict recurrence risk following adjuvant S-1 therapy: Results of an ancillary analysis from a phase III trial of resected biliary tract cancer (JCOG1202A1). Journal of hepato-biliary-pancreatic sciences, 31:886-896, 2024
12. Shimizu Y, Hayashi A, Maeda I, Miura T, Inoue A, Takano M, Aoyama M, Masukawa K, Miyashita M. Resilience and coping styles in family caregivers of terminally ill patients: A cross-sectional survey. Palliative & supportive care, 23:e12, 2024