Annual Report 2019
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 will focus 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 undertaken 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) Practical application of predictive biomarkers for adjuvant chemotherapy
3) Search for biomarkers for pathology and diagnosis of cancer using circulating tumor cells
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. To demonstrate proof of concept for pancreatic cancer screening using biomarkers, we conducted experimental trials for pancreatic cancer using this ELISA kit with the Japan Cancer Society, Kagoshima University, Hokkaido University and others. A proof-of-concept (POC) was conducted on the clinical performance of apoA2-is from this experimental pancreatic cancer screening. More than 13,000 subjects have been enrolled and the results are being analyzed.
2) The National Cancer Institute Canadian 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.
3) We have established a new method for collecting circulating tumor cells (CTCs) with the National University of Singapore. In addition, we succeeded in analyzing metabolites from one cell of CTCs obtained by the collecting method in collaboration with RIKEN. It was clarified that metabolite profiles differ between different cancer types. Furthermore, we tried a comparative analysis of genomic mutations between CTCs and cell-free DNA in blood. It was revealed that some genomic mutations are differences between CTCs and cell-free DNA even from the same patient.
Clinical trials
Experimental screening for pancreatic cancer in Kagoshima and Hokkaido Prefectures.
Future prospects
1) The aim of the study is to develop efficient screening methods for pancreatic cancer.
2) 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. It is expected that IVD will allow efficient treatment selection for patients with stage-I NSCLC.
3) From CTCs, we try to find metabolite profiles and genomic mutations that correlate treatment effects. We will develop new biomarkers using these profiles.
List of papers published in 2019
Journal
1. Nambu M, Masuda T, Ito S, Kato K, Kojima T, Daiko H, Ito Y, Honda K and Ohtsuki S. Leucine-Rich Alpha-2-Glycoprotein 1 in Serum Is a Possible Biomarker to Predict Response to Preoperative Chemoradiotherapy for Esophageal Cancer. Biol Pharm Bull, 2019. 42(10): 1766-1771. PMID: 31582665 DOI: 10.1248/bpb.b19-00395
2. Suzuki T, Yamazaki H, Honda K, Ryo E, Kaneko A, Ota Y and Mori T. Altered DNA methylation is associated with aberrant stemness gene expression in earlystage HNSCC. Int J Oncol, 2019. 55(4): 915-924. PMID: 31432153 DOI: 10.3892/ijo.2019.4857
3. Onidani K, Shoji H, Kakizaki T, Yoshimoto S, Okaya S, Miura N, Sekikawa S, Furuta K, Lim CT, Shibahara T, Boku N, Kato K and Honda K. Monitoring of cancer patients via next-generation sequencing of patient-derived circulating tumor cells and tumor DNA. Cancer Sci, 2019. 110(8): 2590-2599. PMID: 31169336 DOI: 10.1111/cas.14092
4. Kobayashi T and Honda K. Trends in biomarker discoveries for the early detection and risk stratification of pancreatic cancer using omics studies. Expert Rev Mol Diagn, 2019. 2019. 19(8):651-654. PMID: 31298060 DOI: 10.1080/14737159.2019.1643718
5. Iemoto T, Nishiumi S, Kobayashi T, Fujigaki S, Hamaguchi T, Kato K, Shoji H, Matsumura Y, Honda K and Yoshida M. Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer. Oncol Lett, 2019. 17(1): 831-842. PMID: 30655836 DOI: 10.3892/ol.2018.9731
6. Nishiumi S, Fujigaki S, Kobayashi T, Kojima T, Ito Y, Daiko H, Kato K, Shoji H, Kodama Y, Honda K and Yoshida M. Metabolomics-based Discovery of Serum Biomarkers to Predict the Side-effects of Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma. Anticancer Res, 2019. 39(1): 519-526. PMID: 30591504 DOI: 10.21873/anticanres.13143
7. Abouleila Y, Onidani K, Ali A, Shoji H, Kawai T, Lim CT, Kumar V, Okaya S, Kato K, Hiyama E, Yanagida T, Masujima T, Shimizu Y and Honda K. Live single cell mass spectrometry reveals cancer-specific metabolic profiles of circulating tumor cells. Cancer Sci, 2019. 110(2):697-706. PMID: 30549153 DOI: 10.1111/cas.13915
8. Honda K, Katzke VA, Husing A, Okaya S, Shoji H, Onidani K, Olsen A, Tjonneland A, Overvad K, Weiderpass E, Vineis P, Muller D, Tsilidis KK, Palli D, Pala V, Tumino R, Naccarati A, Panico S, Aleksandrova K, Boeing H, Bueno-de-Mesquita HB, Peeters PH, Trichopoulou A, Lagiou P, Khaw KT, Wareham NJ, Travis RC, Merino S, Duell EJ, Rodriguez-Barranco M, Chirlaque MD, Barricarte A, Rebours V, Boutron-Ruault MC, Romana Mancini F, Brennan P, Scelo G, Manjer J, Sund M, Ohlund D, Canzian F and Kaaks R. CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation. Int J Cancer, 2019. 144(8):1877-1887. PMID: 30259989 DOI: 10.1002/ijc.31900
9. Kato S and Honda K. CA19-9 as a therapeutic target in pancreatitis. Ann Transl Med, 2019. 7(Suppl 8): S318. PMID: 32016036 DOI: 10.21037/atm.2019.09.161