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Small cell lung carcinoma biomarker panel

A technology for lung cancer and cytokeratin, which is applied in the fields of treatment and prevention, cancer diagnosis, and prognosis, and can solve problems such as undetermined prognostic predictors.

Inactive Publication Date: 2011-06-01
MUBIO PRODS BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date, no suite of clinically based prognostic predictors has been identified that yields satisfactory results

Method used

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  • Small cell lung carcinoma biomarker panel
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  • Small cell lung carcinoma biomarker panel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0102] Example 1: Experiments examining the differential expression of NCAM 180 (NCAM exon 180) in various cell lineages.

[0103] Differential expression of NCAM-180 was assessed in different cancer cell lines and healthy controls using known technical procedures including:

[0104] - RNA extraction and cDNA synthesis according to standard protocols; and

[0105] -according to figure 1 PCR amplification was performed to assess the expression of NCAM exon 18 according to the principle shown.

[0106] As part of NCAM-180, expression of NCAM exon 18 was found in cell cultures from neuroendocrine tumors (SH-SYSY and CCI), especially in small cell lung cancer (SCLC) cell lines overexpression of ( figure 2 ). Expression of the NCAM 180 kDa splice variant was not found in peripheral blood mononuclear cells (PBMCs) of healthy controls. The results of other cell lines are shown in Table 1.

[0107]

[0108]

Embodiment 2

[0109] Example 2: Serum markers for neuroendocrine differentiation of lung tumors

[0110] a. Detection of NCAM antigen in human serum samples.

[0111] NCAM, including the splice variants NCAM 120, 140, and 180, is a neuroendocrine differentiation marker. NCAM is expressed in all small cell lung cancers (SCLC) and 20% of non-small cell lung cancers (NSCLC). In addition, all tumors with features of neuroendocrine differentiation, natural killer (NK) cells comprising 10% of the total peripheral blood mononuclear cells (PBMC) and NCAM expression in the NSCLC stroma were also characterized. On the other hand, in normal lung tissue, NCAM expression was found only sporadically. In this experiment, we found that NCAM antigen could be detected in the serum of patients with neuroendocrine differentiated tumors (SCLC serum (N=7, PromedDx)), while in the healthy control group (N=7, healthy volunteers) NCAM antigen was not found in the sera. We used a sandwich ELISA to measure the se...

Embodiment 3

[0122] Example 3: Experiment to measure serum levels of NCAM 180 / NCAM exon 18-antigen.

[0123]NCAM exon 18 is specifically expressed in the NCAM 180 KDa splice variant of the NCAM protein. NCAM exon 18 is specifically expressed in the cytoplasmic tail of the transmembrane glycoprotein NCAM. This NCAM splice variant is specific for SCLC (see PCT publication WO2007-104511). With this assay, we demonstrate that NCAM exon 18-antigen can be detected in the sera of SCLC patients, and that NCAM exon 18 in the sera of SCLC patients (N=7) - Antigen titers are much higher. These data suggest that NCAM exon 18 serum antigen titers can be used as a biomarker for SCLC diagnosis. A sandwich ELISA was used to measure NCAM exon 18-tumor antigen levels in serum samples. SCLC serum samples (N=7, stage 3a (N=2), stage 3b (N=1), stage 4 (N=3) and extended disease stage (N=1)) were obtained from PromedDx, and control serum was isolated from healthy Clotted blood obtained from volunteers (smo...

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Abstract

The invention relates generally to the field of cancer detection, diagnosis, subtyping, staging, prognosis, treatment and prevention. More particularly, the present invention relates to methods for the detection, and / or diagnosing and / or subtyping and / or staging of lung cancer in a patient. Based on a particular panel of biomarkers, the present invention provides methods to detect, diagnose at an early stage and / or differentiate small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) and within NSCLC to differentiate between squamous cell carcinomas (SCC), adenocarcinomas (AC), within SCC to discriminate G2 and G3 stage and within lung cancer to differentiate for lung cancers with or without neuroendocrine origin. It further provides the use of said panel of biomarkers in monitoring disease progression in a patient, including both in vitro and in vivo imaging techniques. The in vitro imaging techniques typically include an immunoassay detecting protein or antibody of the biomarkers on a sample taken from said patient, e.g. serum or tissue sample. The in vivo imaging techniques typically include chest radiographs (X-rays), Computed Tomography (CT) imaging, spiral CT, Positron Emission Tomography (PET), PET-CT and scintigraphy for molecular imaging and diagnosis and to monitor disease progression and treatment response in patients. It is accordingly a further aspect to provide a kit to perform the aforementioned diagnosing and / or subtyping and / or staging assay and the imaging techniques, comprising reagents to determine the gene expression or protein level of the aforementioned panel of biomarkers for in vitro and in vivo applications.

Description

field of invention [0001] The present invention is generally relevant to the fields of cancer diagnosis, prognosis, treatment and prevention. More specifically, the invention relates to methods of typing lung cancer in a patient. The present invention provides a method for (early) diagnosis of lung cancer, a method for distinguishing small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC), and a method for distinguishing squamous cell carcinoma (SCC) in NSCLC, based on a specific set of biomarkers , adenocarcinoma (AC) and eventually large cell carcinoma, methods to distinguish lung cancers with or without neuroendocrine origin, methods to distinguish SCC tumors in G2 and G3 stages, and methods to determine the degree of heterogeneity in lung cancers. [0002] The present invention also provides the use of the above-mentioned biomarker panel in monitoring the progress of a patient's disease, including in vitro and in vivo imaging techniques. In vitro imaging te...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574
CPCG01N33/57423B82Y15/00G01N2333/705
Inventor A·梵德博尔吉特F·C·S·拉马克斯S·M·梵登艾杰德M·哈姆斯马F·W·法尔肯贝格K·斯图尔G·普驰曼H·E·梅尔G·科洛普
Owner MUBIO PRODS BV
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