論文 - 金井　弥栄

Method for prognosis of renal cell carcinoma

Y Kanai, E Arai, Y Tian

US Patent App. 16/708,879 2020年

Method for prognosis of renal cell carcinoma

Y Kanai, E Arai, Y Tian

US Patent App. 16/708,879 2020年

Method for prognosis of renal cell carcinoma

Y Kanai, E Arai, Y Tian

US Patent App. 16/708,879 2020年

Method for evaluating risk of hepatocellular carcinoma

Y Kanai, E Arai, T Yotani, E Sunamura

US Patent App. 16/637,076 2020年

Method for evaluating risk of hepatocellular carcinoma

Y Kanai, E Arai, T Yotani, E Sunamura

US Patent App. 16/637,076 2020年

Method for evaluating risk of hepatocellular carcinoma

Y Kanai, E Arai, T Yotani, E Sunamura

US Patent App. 16/637,076 2020年

Infiltration of tumor‐associated macrophages is involved in tumor programmed death‐ligand 1 expression in early lung adenocarcinoma

T Shima, M Shimoda, T Shigenobu, T Ohtsuka, T Nishimura, K Emoto, ...

Cancer science 111 （ 2 ） 727 2020年

最終著者

Cooperative participation of epigenomic and genomic alterations in the clinicopathological diversity of gastric adenocarcinomas: significance of cell adhesion and epithelial …

M Yang, E Arai, Y Takahashi, H Totsuka, S Chiku, H Taniguchi, H Katai, ...

Carcinogenesis 41 (11), 1473-1484 2020年

Cooperative participation of epigenomic and genomic alterations in the clinicopathological diversity of gastric adenocarcinomas: significance of cell adhesion and epithelial …

M Yang, E Arai, Y Takahashi, H Totsuka, S Chiku, H Taniguchi, H Katai, ...

Carcinogenesis 41 (11), 1473-1484 2020年

Candidate molecules as diagnostic biomarker for human uterine mesenchymal tumors

T Hayashi, K Sano, T Ichimura, G Gur, P Yaish, D Zharhary, Y Kanai, ...

Annals of Cytology and Pathology 5 (1), 054-057 2020年

腫瘍 部位別 腎細胞癌: 病理診断

S MIKAMI, ERI ARAI, YAE KANAI

臨床泌尿器科 74 (4), 10-15 2020年

Profiling of Target Molecules for Immunotherapy in Mesenchymal Tumors.

Hayashi T, Ichimura T, Sano K, Tonegawa S, Kanai Y, Zharhary D, Aburatani H, Yaegashi N, Konishi I

Journal of clinical medicine research 11 （ 8 ） 609 - 613 2019年08月

共著, 査読有り,  ISSN  1918-3003

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Genome-wide DNA methylation profile of early-onset endometrial cancer: Its correlation with genetic aberrations and comparison with late-onset endometrial cancer

Makabe T., Arai E., Hirano T., Ito N., Fukamachi Y., Takahashi Y., Hirasawa A., Yamagami W., Susumu N., Aoki D., Kanai Y.

Carcinogenesis （Carcinogenesis）  40 （ 5 ） 611 - 623 2019年07月

研究論文（学術雑誌）, 共著, 最終著者, 査読有り,  ISSN  01433334

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© 2019 The Author(s) 2019. Published by Oxford University Press. The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among 'transcriptional factors'. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

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Integrated analysis of genetic and epigenetic alterations in gastric carcinomas

Yang Menghan, Arai Eri, Sakamoto Hiromi, Totsuka Hirohiko, Taniguchi Hirokazu, Katai Hitoshi, Yoshida Teruhiko, Kanai Yae

CANCER RESEARCH 79 （ 13 ）  2019年07月

最終著者,  ISSN  0008-5472

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Establishment of permutation for cancer risk estimation in the urothelium based on genome-wide DNA methylation analysis.

Tsumura K, Arai E, Tian Y, Shibuya A, Nishihara H, Yotani T, Yamada Y, Takahashi Y, Maeshima AM, Fujimoto H, Nakagawa T, Kume H, Homma Y, Yoshida T, Kanai Y.

Carcinogenesis （Carcinogenesis）  40 （ 11 ） 1308 - 1319 2019年06月

研究論文（学術雑誌）, 共著, 最終著者, 査読有り,  ISSN  0143-3334

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© 2019 The Author(s). Published by Oxford University Press. All rights reserved. The aim of this study was to establish permutation for cancer risk estimation in the urothelium. Twenty-six samples of normal control urothelium obtained from patients without urothelial carcinomas (C), 47 samples of non-cancerous urothelium without noticeable morphological changes obtained from patients with urothelial carcinomas (N), and 46 samples of the corresponding cancerous tissue (T) in the learning cohort and 64 N samples in the validation cohort, i.e. 183 tissue samples in total, were analyzed. Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation 450K BeadChip, and DNA methylation levels were verified using pyrosequencing and MassARRAY. Amplicon sequencing was performed using the GeneRead DNAseq Targeted Panels V2. Although N samples rarely showed genetic mutations or copy number alterations, they showed DNA methylation alterations at 2502 CpG sites compared to C samples, and such alterations were inherited by or strengthened in T samples, indicating that DNA methylation alterations may participate in field cancerization in the urothelium. Receiver operating characteristic curve analysis confirmed the feasibility of cancer risk estimation to identify urothelium at the precancerous stage by DNA methylation quantification. Cancer risk estimation permutation was established using a combination of two marker CpG loci on the HOXC4, TENM3 and TLR1 genes (sensitivity and specificity 96-100%). Among them, the diagnostic impact of 10 patterns of permutation was successfully validated in the validation cohort (sensitivity and specificity 94-98%). These data suggest that cancer risk estimation using procedures such as urine tests during health checkups might become applicable for clinical use.

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Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer

Kikuchi-Koike R., Nagasaka K., Tsuda H., Ishii Y., Sakamoto M., Kikuchi Y., Fukui S., Miyagawa Y., Hiraike H., Kobayashi T., Kinoshita T., Kanai Y., Shibata T., Imoto I., Inazawa J., Matsubara O., Ayabe T.

BMC Cancer （BMC Cancer）  19 （ 1 ） 521 - 521 2019年05月

研究論文（学術雑誌）, 共著

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© 2019 The Author(s). Background: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. Methods: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. Results: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69%, 9 of 13) in group 1, luminal B-like (57%, 13 of 23) and HER2-overexpressing (26%, 6 of 23) subtypes in group 2, and luminal A-like subtype (60%, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). Conclusions: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.

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Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma

Saito Y., Muramatsu T., Kanai Y., Ojima H., Sukeda A., Hiraoka N., Arai E., Sugiyama Y., Matsuzaki J., Uchida R., Yoshikawa N., Furukawa R., Saito H.

Cell Reports （Cell Reports）  27 （ 4 ） 1265 - 1276.e4 2019年04月

共著,  ISSN  2211-1247

　概要を見る

© 2019 The Author(s) Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids revealed that SOX2 could be a potential prognostic biomarker for patients with BTC. We screened a compound library consisting of drugs used clinically for their ability to suppress organoids derived from BTCs and found that the antifungal drugs amorolfine and fenticonazole significantly suppressed the growth of organoids derived from BTCs with minimal toxicity to normal biliary epithelial cells. Patient-derived organoids may be a powerful research tool for the clarification of molecular pathogenesis and the discovery of biomarkers and therapeutic drugs for refractory cancers.

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Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features

Hatano M., Ojima H., Masugi Y., Tsujikawa H., Hiraoka N., Kanai Y., Shimada K., Shinoda M., Sakamoto M.

Human Pathology （Human Pathology）  86   222 - 232 2019年04月

研究論文（学術雑誌）, 共著,  ISSN  00468177

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© 2018 Elsevier Inc. We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.

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Clinical and endoscopic findings to assist the early detection of duodenal adenoma and adenocarcinoma

Matsuzaki J., Suzuki H., Shimoda M., Mori H., Fukuhara S., Miyoshi S., Masaoka T., Iwao Y., Kanai Y., Kanai T.

United European Gastroenterology Journal （United European Gastroenterology Journal）  7 （ 2 ） 250 - 260 2019年03月

共著,  ISSN  20506406

　概要を見る

© Author(s) 2018. Background: Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis. Objective: A case-control study was designed to evaluate the clinical and endoscopic characteristics of patients with nonampullary duodenal epithelial tumours (NADETs). Methods: Patients with NADETs were chronologically divided into a discovery and a validation sets. Two age- and sex-matched control individuals for each case in the discovery set were randomly selected from individuals without NADET. A prediction model for the presence of NADET, constructed in the discovery set, was evaluated in the validation set. Results: In total, 368 adenomas, 81 adenocarcinomas, and 314 controls were analysed. Current smoking, Barrett oesophagus, fundic gland polyps, history of malignant disease, and absence of dyslipidaemia were independently associated with the presence of NADET. The combination of these five factors enabled significant discrimination for NADET in the bulb with a sensitivity of 0.81 in the validation set. We also showed that duodenal adenocarcinomas in the bulb had greater invasive potential than adenocarcinomas in the second portion. Conclusion: The presence of a duodenal tumour in the bulb could be predicted by clinical and endoscopic findings, which helps improve the prognosis and quality of life of patients.

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Prospective exosome-focused translational research for afatinib study of non-small cell lung cancer patients expressing EGFR (EXTRA study)

Okuma Y., Morikawa K., Tanaka H., Yokoyama T., Itani H., Horiuchi K., Nakagawa H., Takahashi N., Bessho A., Soejima K., Kishi K., Togashi A., Kanai Y., Ueda K., Horimoto K., Matsutani N., Seki N.

Thoracic Cancer （Thoracic Cancer）  10 （ 2 ） 395 - 400 2019年02月

共著, 査読有り,  ISSN  17597706

　概要を見る

© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd Patients with EGFR-mutated non-small cell lung cancer (NSCLC) exhibit resistance to EGFR-tyrosine kinase inhibitors (TKIs) within 9–14 months of therapy. Recently, EGFR-mutated NSCLC has demonstrated the potential for heterogeneity; therefore, the manner of clonal heterogeneity may impact the duration of progression-free and overall survival and other parameters affecting EGFR-TKI treatment efficacy. However no predictive biomarker of these favorable treatment efficacies has been identified to date. The exosome-focused translational research for afatinib (EXTRA) study aims to identify a novel predictive biomarker and a resistance marker for afatinib by analyzing data from association studies of the clinical efficacy of afatinib and four “OMICs” (genomics, proteomics, epigenomics, and metabolomics) using peripheral blood from patients treated with afatinib. This study aims to: (i) conduct comprehensive multi-OMIC analyses in a prospective clinical trial, and (ii) focus on both sera/plasma and exosome as a source for OMIC analyses to identify a novel predictor of the efficacy of a specific drug. To eliminate the carryover bias of prior treatment, systemic treatment-naïve patients were enrolled. The candidates to be screened for biomarkers comprise a discovery cohort of 60 patients and an independent validation cohort of 40 patients. The EXTRA study is the first trial to screen novel biomarkers of longer treatment efficacy of EGFR-TKIs using four-OMICs analyses, focusing on both “naked or free” molecules and “capsulated” exosomal components in serially collected peripheral blood.

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