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JP-7854661-B2 - Methods for detecting colorectal tumors

JP7854661B2JP 7854661 B2JP7854661 B2JP 7854661B2JP-7854661-B2

Inventors

  • 山田 拓司
  • 福田 真嗣
  • 谷内田 真一

Assignees

  • 国立大学法人東京科学大学
  • 慶應義塾
  • 国立研究開発法人国立がん研究センター

Dates

Publication Date
20260507
Application Date
20210607
Priority Date
20200605

Claims (7)

  1. A method for detecting colorectal tumors, characterized by comprising the following steps (1) to (3): (1) A step of measuring the amount of microorganisms in the feces of a subject, wherein the microorganism is at least one microorganism selected from the group consisting of Actinomyces odontolyticus, Phascolarctobacterium succinatutens, Actinomyces viscosus, Desulfovibrio longreachensis, Solobacterium moorei, Gemella morbillorum, and Bifidobacterium longum subsp. longum. (2) A step of comparing the value measured in step (1) with the corresponding value in the feces of a healthy person. (3) As a result of the comparison in step (2), if the value measured in step (1) is the amount of Actinomyces odontolyticus, Phascolarctobacterium succinatutens, Actinomyces viscosus, Desulfovibrio longreachensis, Solobacterium moorei, or Gemella morbillorum, the subject is determined to have a colorectal tumor if the value is higher than the corresponding value in the stool of a healthy person; if the value measured in step (1) is the amount of Bifidobacterium longum subsp. longum, the subject is determined to have a colorectal tumor if the value is lower than the corresponding value in the stool of a healthy person.
  2. The method for detecting colorectal tumors according to claim 1, characterized in that, in step (1), the microorganism is at least one microorganism selected from the group consisting of Actinomyces odontolyticus, Phascolarctobacterium succinatutens, Actinomyces viscosus, and Desulfovibrio longreachensis, and in step (3), the subject is determined to have a colorectal tumor when the value measured in step (1) is higher than the corresponding value in the feces of a healthy person.
  3. The method for detecting colorectal tumors according to claim 1, characterized in that in step (1), the microorganism is Actinomyces odontolyticus, and in step (3), the subject is determined to have a colorectal tumor when the value measured in step (1) is higher than the corresponding value in the feces of a healthy person.
  4. Furthermore, the method for detecting colorectal tumors according to any one of claims 1 to 3, characterized in that it further includes the following steps (a-1) to (a-3), (a-1) A step of measuring the amount of amino acids in the feces of a subject, wherein the amino acid is at least one amino acid selected from the group consisting of isoleucine, leucine, valine, phenylalanine, tyrosine, glycine, and serine. (a-2) A step of comparing the value measured in step (a-1) with the corresponding value in the feces of a healthy person. (a-3) A step in which, as a result of the comparison in step (a-2), if the value measured in step (a-1) is higher than the corresponding value in the stool of a healthy person, the subject is determined to have a colorectal tumor.
  5. Furthermore, the method for detecting colorectal tumors according to any one of claims 1 to 3, characterized in that it further includes the following steps (b-1) to (b-3), (b-1) A step of measuring the amount of organic acid in the feces of a subject, wherein the organic acid is at least one organic acid selected from the group consisting of succinic acid, fumaric acid, malic acid, and isovaleric acid. (b-2) A step of comparing the value measured in step (b-1) with the corresponding value in the feces of a healthy person. (b-3) A step in which, as a result of the comparison in step (b-2), if the value measured in step (b-1) is higher than the corresponding value in the stool of a healthy person, the subject is determined to have a colorectal tumor.
  6. Furthermore, the method for detecting colorectal tumors according to any one of claims 1 to 3, characterized in that it further includes the following steps (c-1) to (c-3), (c-1) A step of measuring the amount of bile acid in the feces of a subject, wherein the bile acid is at least one bile acid selected from the group consisting of deoxycholic acid, glycocholic acid, and taurocholic acid. (c-2) A step of comparing the value measured in step (c-1) with the corresponding value in the feces of a healthy person. (c-3) A step in which, as a result of the comparison in step (c-2), if the value measured in step (c-1) is higher than the corresponding value in the stool of a healthy person, the subject is determined to have a colorectal tumor.
  7. A method for detecting a colorectal tumor according to any one of claims 1 to 6, characterized in that the colorectal tumor is an adenoma or an intramucosal carcinoma.

Description

Article 30, Paragraph 2 of the Patent Act applies October 10, 2020 Announced at keystone symposia, Microbiome: Therapeutic Implications (T1) Article 30, Paragraph 2 of the Patent Act applies January 26, 2020 Announced at the 7th US-Japan Workshop on Biomarkers for Cancer Early Detection Applicable to Article 30, Paragraph 2 of the Patent Law. Presented at the 4th Academia Exchange Meeting of the Japan Microbiome Consortium on January 17, 2020. Application of Article 30, Paragraph 2 of the Patent Act Announced at RWBC-OIL Monthly Seminar on January 16, 2020 Article 30, Paragraph 2 of the Patent Act applies February 19, 2020 Presented at The 4th International Symposium of Kyoto Biomolecular Mass Spectrometry Society Applicable to Article 30, Paragraph 2 of the Patent Law. Publisher: The Japanese Society for Intestinal Microbiota. Publication: Journal of Intestinal Microbiota, Vol. 34, No. 2, 2020, p. 56. Publication date: May 20, 2020. Applicable to Article 30, Paragraph 2 of the Patent Law. Publisher: Japanese Society of Oral and Maxillofacial Surgeons. Publication Name: Oral and Maxillofacial Surgery Hand Manual for General Clinicians and Oral and Maxillofacial Surgeons '19, pp. 230-237. Publication Date: July 10, 2019. Applicable to Article 30, Paragraph 2 of the Patent Law. Publisher: Yodosha Publication: Experimental Medicine, May 2020 Issue, Vol. 38, No. 8, Latest Findings Obtained Using Multi-Omics, pp. 1306-1312, Published on April 20, 2020. Applicable under Article 30, Paragraph 2 of the Patent Law. Publisher: Farm Press Co., Ltd. Publication: Small Animal Clinical Journal mVm, May 2020 Issue, No. 190, pp. 23-30. Publication Date: May 1, 2020. Applicable under Article 30, Paragraph 2 of the Patent Law. Publisher: The Japanese Cancer Association. Publication Name: Abstracts of the 78th Annual Meeting of the Japanese Cancer Association. Publication Date: September 5, 2019. Applicable to Article 30, Paragraph 2 of the Patent Law. Presented at the 78th Annual Meeting of the Japanese Cancer Association on September 28, 2019. Article 30, Paragraph 2 of the Patent Act applies Publication name: Cancer Science 2020 111 766-773 Publication date: Published on January 7, 2020 Applicable to Article 30, Paragraph 2 of the Patent Law. Publication name: Nature Medicine VOL 25 JUNE 2019 968-976 Publication date: June 7, 2019. Applicable under Article 30, Paragraph 2 of the Patent Law. Announced on June 7, 2019, at https://www.amed.go.jp/news/release_20190607-01.html Applicable under Article 30, Paragraph 2 of the Patent Law. Announced on June 7, 2019, at https://www.titech.ac.jp/news/2019/044404.html. Applicable to Article 30, Paragraph 2 of the Patent Law. Presented at the 92nd Annual Meeting of the Japanese Biochemical Society on September 18, 2019. Applicable to Article 30, Paragraph 1 of the Patent Law. Presented at the 93rd Annual Meeting of the Japanese Society for Bacteriology on February 19, 2020. This invention relates to a method for detecting colorectal tumors such as adenomas and intramucosal carcinomas. If colorectal cancer can be detected at a stage before it becomes advanced, the mortality rate of patients can be reduced, and the cancer can be removed endoscopically, thereby improving the quality of life for patients. Colorectal cancer has surpassed stomach cancer to become the most common cancer in Japan. While the Westernization of lifestyle habits, including diet, is thought to be the cause, the exact mechanism remains unclear. The number of cells in a single human being is approximately 37 trillion, and the number of gut bacteria per person is said to be around 40 trillion, weighing approximately 1 to 1.5 kg. Recently, it has become clear that disruptions in this gut microbiota are related to various diseases, including inflammatory bowel disease. In 2012, it was reported that Fusobacterium nucleatum, known as a causative agent of periodontal disease in the oral cavity, is characteristically present in large numbers in the stool of colorectal cancer patients, and this has been verified (Non-Patent Literature 1, Non-Patent Literature 2). Castellarin, M. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22, 299-306 (2012).Kostic, A. D. et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22, 292-298 (2012). Figure showing global metagenomic and metabolomic characteristics of fecal samples.A diagram illustrating the different taxonomic and metabolomic signatures of cancer as it progresses through each stage.Diagram showing CRC-related changes in microbial genes grouped into KO genes and KEGG pathway modules.A diagram illustrating the dynamics of microorganisms and their diagnostic potential during the multi-stage progression of CRC.A diagram outlining the research and the metagenomic analysis pipeline.A diagram showing the clinical information of the subjects.A diagram showing the microbial community struc