Lung cancer differential marker

Patent metadata

Field	Value
Publication number	US-9696320-B2
Application number	US-201113823922-A
Country	US
Kind code	B2
Filing date	Sep 9, 2011
Priority date	Sep 17, 2010
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

An object of the present invention is to develop and provide a lung cancer differential marker with which lung cancer can be diagnosed conveniently and highly sensitively without depending only on increase or decrease in protein expression level between cancer patients and healthy persons. Another object of the present invention is to develop and provide a glycan marker capable of distinguishing histological types of lung cancer. Of serum glycoproteins, glycopeptide and glycoprotein groups whose glycan structures were altered specifically in lung cancer cell culture supernatants were identified, and they are provided as lung cancer differential markers.

First claim

The invention claimed is:

1. A method for determining whether a test subject afflicted with lung cancer is afflicted with small cell lung cancer comprising:
(i) detecting a lung cancer differential marker glycoprotein glycosylated with a glycan at an asparagine residue or at least one fragment thereof in a sample obtained from the test subject, and
(ii) determining whether the test subject is afflicted with small cell lung cancer by determining whether the glycoprotein or the fragment thereof is present in the sample;
wherein the presence of the glycoprotein or fragment in the sample indicates that the test subject is afflicted with small cell lung cancer,

and wherein:
(a) the lung cancer differential marker glycoprotein is secretogranin III, and the glycoprotein and the fragment thereof comprise an amino acid sequence selected from the group consisting of SEQ ID NO: 56 and SEQ ID NO: 57, wherein SEQ ID NO: 56 is glycosylated with a glycan at the asparagine residue at position 13 and SEQ ID NO: 57 is glycosylated with a glycan at the asparagine residue at position 6;
(b) the lung cancer differential marker glycoprotein or the fragment thereof is detected using at least one glycan probe that binds to a fucosylated glycan, a high mannose-type glycan, a hybrid-type glycan, or a biantennary complex-type glycan, wherein the glycan probe is AAL lectin and/or ConA lectin, an antibody, or a phage antibody; and
(c) the sample is a body fluid, lung cancer tissue or a lung lavage.

2. The method of claim 1 , wherein the body fluid is pleural effusion, lymph, a cell extract, sputum, or blood comprising serum, plasma and interstitial fluid.

3. A method of distinguishing between small cell lung cancer and lung adenocarcinoma in a test subject afflicted with small cell lung cancer or lung adenocarcinoma, the method comprising:
(i) detecting binding of AAL lectin and/or ConA lectin to a lung cancer differential marker glycoprotein or at least one fragment thereof in a sample obtained from the test subject by contacting the sample with the lectin, and
(ii) determining that the lung cancer in the test subject is small cell lung cancer if the glycoprotein or fragment thereof in the sample acquired from the test subject binds to AAL and/or ConA, or that the lung cancer in the test subject is lung adenocarcinoma if the glycoprotein or fragment thereof in the sample acquired from the test subject does not bind to both AAL and ConA,
wherein the glycoprotein is secretogranin III and the glycoprotein and the fragment thereof comprise an amino acid sequence selected from the group consisting of SEQ ID NO: 56 and SEQ ID NO: 57, wherein SEQ ID NO: 56 is glycosylated with a glycan at the asparagine residue at position 13 and SEQ ID NO: 57 is glycosylated with a glycan at the asparagine residue at position 6;
and wherein the sample is a body fluid, lung cancer tissue or a lung lavage.

4. The method of claim 3 , wherein the body fluid is pleural effusion, lymph, a cell extract, sputum, or blood comprising serum, plasma and interstitial fluid.

Assignees

• Narimatsu Hisashi
• Togayachi Akira
• Ikehara Yuzuru
• Kaji Hiroyuki
• Kuno Atsushi
• Ohkura Takashi
• Matsuzaki Hideki
• Hirao Yoshitoshi
• Iwaki Jun
• Abe Minako
• Nomura Masaharu
• Noguchi Masayuki
• Nat Inst Advanced Ind Science & Tech
• Univ Tokyo Medical

Inventors

• Narimatsu Hisashi
• Togayachi Akira
• Ikehara Yuzuru
• Kaji Hiroyuki
• Kuno Atsushi
• Ohkura Takashi
• Matsuzaki Hideki
• Hirao Yoshitoshi
• Iwaki Jun
• Abe Minako
• Nomura Masaharu
• Noguchi Masayuki

Classifications

• G01N33/575

  for cancer · CPC title

• G01N33/5752

  of the lungs · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K14/4748 Primary

  Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE · CPC title

• G01N2440/38

  addition of carbohydrates, e.g. glycosylation, glycation · CPC title