Annual Report 2020
Department of Biomarkers for Early Detection of Cancer
Kazufumi Honda, Nami Miura, Ayumi Kashiro, Takako Sakamoto, Keiko Takeuchi
Introduction
Using innovative proteomic, metabolic, and genomic techniques, our department focuses its research interests on clarifying the molecular and cellular mechanisms of cancer promotion and progression. With the aim of discovering targets for early cancer detection, molecular therapy, and personalized medicine, we have performed a comprehensive protein, metabolite, and gene expression profiling of various cancer cell lines and cancer tissues, as well as sera/plasma and tissue samples from cancer patients.
The Team and What We Do
1) Practical implementation of effective blood biomarker-based pancreatic cancer screening
2) Search for biomarkers using antibody-based proteomics
3) Practical application of predictive biomarkers for adjuvant chemotherapy
Research activities
1) We have developed an ELISA kit for apolipoprotein-A2 isoforms (apoA2-is) to detect early pancreatic cancer and pancreatic cancer risk diseases. The subjects for the screening study were recruited from the six medical checkup facilities in Japan between October 2015 and January 2017. A total of 5120 subjects in experimental pancreatic cancer screening has been enrolled, and apoA2-is was found to have the potential to enrich pancreatic cancer and high-risk individuals for pancreatic cancer by increasing the diagnostic probability before imaging examinations.
2) As a result of antibody proteomics using an antibody library that consists of 1012 antibodies on tissue microarrays obtained from 182 ovarian cancer patients, we succeeded in identifying a new biomarker that correlates with poor prognosis. Patients with high expression of the biomarker protein, cystathionine-γ-lyase (CSE), were found to have no response to post-operative platinum-based chemotherapy, and the cause was polysulfide produced from CSE. Using surface-enhanced Raman spectroscopy, we could detect polysulfides in cancer tissue. It was also shown that ambroxol degrades polysulfides and increases the sensitivity of platinum-based chemotherapy in vitro and in vivo.
3) The National Cancer Institute of Canada Clinical Trial Group JBR.10 led to the adoption of adjuvant cisplatin-based chemotherapy for patients with resected stages-IB to IIIA non-small cell lung cancer (NSCLC). In the subgroup analysis using a JBR.10 database search, we demonstrated a significant clinical benefit of adjuvant chemotherapy in terms of overall survival only in the actinin-4 (ACTN4) high expression group. The data suggested that ACTN4 is a potential predictive biomarker of the efficacy of adjuvant chemotherapy in early-stage NSCLC patients. We developed a fluorescence in situ hybridization (FISH) test kit to examine the ACTN4 gene amplification. Using this test kit, we are developing an in vitro diagnostic drug that detects the ACTN4 gene amplification and predicts the efficacy of adjuvant chemotherapy.
Future Prospects
1) This study aims to develop efficient screening methods for pancreatic cancer.
2) In chemoresistant ovarian cancer, the use of the biomarker may improve the prognosis through post-operative platinum-based chemotherapy with drug combination.
3) To improve the mortality of non-small cell lung cancer (NSCLC), we are clinically developing in vitro diagnostics (IVD) to predict the efficacy of adjuvant chemotherapy in patients with completely resected stage-I NSCLC. IVD is expected to allow the efficient treatment selection for patients with stage-I NSCLC.
List of papers published in 2020
Journal
1. Kihara T, Yamagishi K, Honda K, Ikeda A, Yatsuya H, Saito I, Kokubo Y, Yamaji T, Shimazu T, Sawada N, Iwasaki M, Iso H, Tsugane S. Apolipoprotein A2 Isoforms in Relation to the Risk of Myocardial Infarction: A Nested Case-Control Analysis in the JPHC Study. J Atheroscler Thromb, 28:483-490, 2021
2. Meng X, Matsumoto F, Mori T, Miura N, Ino Y, Onidani K, Kobayashi K, Matsuzaki Y, Yoshimoto S, Ikeda K, Honda K. BP180 Is a Prognostic Factor in Head and Neck Squamous Cell Carcinoma. Anticancer Res, 41:1089-1099, 2021
3. Honda K, Hishiki T, Yamamoto S, Yamamoto T, Miura N, Kubo A, Itoh M, Chen WY, Takano M, Yoshikawa T, Kasamatsu T, Sonoda S, Yoshizawa H, Nakamura S, Itai Y, Shiota M, Koike D, Naya M, Hayakawa N, Naito Y, Matsuura T, Iwaisako K, Masui T, Uemoto S, Nagashima K, Hashimoto Y, Sakuma T, Matsubara O, Huang W, Ida T, Akaike T, Masugi Y, Sakamoto M, Kato T, Ino Y, Yoshida H, Tsuda H, Hiraoka N, Kabe Y, Suematsu M. On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity. Redox Biol, 41:101926, 2021
4. Sugano T, Yoshida M, Masuda M, Ono M, Tamura K, Kinoshita T, Tsuda H, Honda K, Gemma A, Yamada T. Prognostic impact of ACTN4 gene copy number alteration in hormone receptor-positive, HER2-negative, node-negative invasive breast carcinoma. Br J Cancer, 122:1811-1817, 2020
5. Abe Y, Hirano H, Shoji H, Tada A, Isoyama J, Kakudo A, Gunji D, Honda K, Boku N, Adachi J, Tomonaga T. Comprehensive characterization of the phosphoproteome of gastric cancer from endoscopic biopsy specimens. Theranostics, 10:2115-2129, 2020
6. Xu X, Honda K, Miura N, Hori S, Le Blanc S, Bergmann F, Gaida MM, Volkmar M, Schimmack S, Hackert T, Strobel O, Felix K. Actinin-4 splice variant - a complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms. J Cancer, 11:2318-2328, 2020
7. Sakamoto S, Komatsu T, Watanabe R, Zhang Y, Inoue T, Kawaguchi M, Nakagawa H, Ueno T, Okusaka T, Honda K, Noji H, Urano Y. Multiplexed single-molecule enzyme activity analysis for counting disease-related proteins in biological samples. Sci Adv, 6:eaay0888, 2020
8. Aoki M, Shoji H, Kashiro A, Takeuchi K, Shimizu Y, Honda K. Prospects for Comprehensive Analyses of Circulating Tumor Cells in Tumor Biology. Cancers (Basel), 12:2020
9. Kato S, Honda K. Use of Biomarkers and Imaging for Early Detection of Pancreatic Cancer. Cancers (Basel), 12:2020
10. Yokose T, Kabe Y, Matsuda A, Kitago M, Matsuda S, Hirai M, Nakagawa T, Masugi Y, Hishiki T, Nakamura Y, Shinoda M, Yagi H, Abe Y, Oshima G, Hori S, Nakano Y, Honda K, Kashiro A, Morizane C, Nara S, Kikuchi S, Shibahara T, Itonaga M, Ono M, Minegishi N, Koshiba S, Yamamoto M, Kuno A, Handa H, Sakamoto M, Suematsu M, Kitagawa Y. O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer. Cancers (Basel), 12:2020
11. Sato Y, Kobayashi T, Nishiumi S, Okada A, Fujita T, Sanuki T, Kobayashi M, Asahara M, Adachi M, Sakai A, Shiomi H, Masuda A, Yoshida M, Takeuchi K, Kodama Y, Kutsumi H, Nagashima K, Honda K. Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer. Cancers (Basel), 12:2020