Biomarker for typing non-small cell lung cancer, and application thereof

A non-small cell lung cancer, biomarker technology, applied in the field of medical detection, can solve the problem of pathological judgment error, poor differentiation and other problems

Active Publication Date: 2021-07-30
深圳康华君泰生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While the limited number of tissue samples and the need to evaluate an increasing number of therapeutically targeted markers has greatly increased current diagnostic needs, studies of histological diagnostic reproducibility have shown intra- and inter-pathologist variability: Wrong results of pathological judgment, poorly differentiated tumors and contradictory immunohistochemical results, etc., pose challenges to the accuracy of precision medicine in lung cancer

Method used

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  • Biomarker for typing non-small cell lung cancer, and application thereof
  • Biomarker for typing non-small cell lung cancer, and application thereof
  • Biomarker for typing non-small cell lung cancer, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Based on the public database, the preliminary screening of variant gene markers for pathological subtypes of non-small cell lung cancer includes the following steps:

[0045] 1. Screening of candidate mutation sites.

[0046] Whole-genome sequencing data of tumor tissues of patients with non-small cell tumors were obtained from the TCGA database (https: / / portal.gdc.cancer.gov / ): In this study, a total of 561 patients with non-small cell lung cancer (including 286 cases of adenocarcinoma and 286 cases of adenocarcinoma) were downloaded. 275 cases of squamous cell carcinoma) whole genome sequencing data, four different software (mutect, varscan, muse and somaticsniper) were used to calculate the mutation sites respectively, and at least two of the four mutation software were used to simultaneously call the mutation sites in the samples as candidates mutation site.

[0047] 2. Potential marker screening.

[0048] Difference analysis was performed based on the adenocarcin...

Embodiment 2

[0053] In this embodiment, the potential markers obtained above are analyzed and verified on clinical samples, including the following steps:

[0054] 1. Tissue sample acquisition:

[0055] The related FFPE section samples of 374 cases of non-small cell lung cancer (191 cases of adenocarcinoma and 183 cases of squamous cell carcinoma) were collected from Jinan University.

[0056] 2. Sample sequencing analysis:

[0057] FFPE tissue samples were analyzed by whole genome sequencing by a third party (Clearcode Biotechnology).

[0058] 3. Model establishment.

[0059] 3.1 The model is initially established.

[0060] Using all the potential markers obtained in Example 1 above, the independent verification set, that is, the above-mentioned 191 cases of adenocarcinoma and 183 cases of squamous cell carcinoma of non-small cell lung cancer patient tissue samples were detected and judged, and the random forest model was used for modeling analysis ( R package randomForest), according...

Embodiment 3

[0068] Select 13 cases of non-small cell lung cancer clinically judged as non-small cell lung cancer samples from Jinan University, which are different from the sample set in Example 2, and use the 20 MARKER combined models established in Example 2 above for analysis, and compare the analysis results with clinical experts The judgment results are compared, and the results are shown in the table below.

[0069] Table 2. Clinical validation results

[0070] cases Model typing results Expert Judgment Results number 1 Adenocarcinoma Adenocarcinoma number 2 squamous cell carcinoma squamous cell carcinoma number 3 Adenocarcinoma squamous cell carcinoma No 4 squamous cell carcinoma Adenocarcinoma Number 5 Adenocarcinoma Adenocarcinoma number 6 Adenocarcinoma Adenocarcinoma Number 7 squamous cell carcinoma squamous cell carcinoma number 8 Adenocarcinoma Adenocarcinoma No.9 squamous cell carcino...

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Abstract

The invention relates to a biomarker for typing non-small cell lung cancer, and application thereof, and belongs to the technical field of medical detection. The biomarker comprises at least five genes such as TP53, STK11, PTEN, NFE2L, KRAS and the like. When squamous cell carcinoma and adenocarcinoma in small cell carcinoma of lung are subjected to typing by utilizing the biomarker, the AUC of a typing diagnosis ROC curve is 0.700 when the at least five markers are used, the AUC of the typing diagnosis ROC curve is 0.734 when the number of the markers is further increased to 10, and the AUC can reach 0.786 when all the biomarkers are used, so that the biomarkers have excellent diagnosis capability.

Description

technical field [0001] The invention relates to the technical field of medical detection, in particular to a biomarker for non-small cell lung cancer typing and its application. Background technique [0002] Lung cancer is a heterogeneous disease. The main basis for the selection of existing lung cancer treatment methods is pathological classification and staging diagnosis. Pathological typing is generally determined by histology: important typing such as: small cell vs non-small cell, adenocarcinoma vs squamous cell carcinoma, etc. The distinction between various morphological subtypes of lung cancer is necessary to guide patient management. Different pathological subtypes have different corresponding treatment strategies. For example, small cell undifferentiated lung cancer is highly malignant and easy to metastasize in the early stage , sensitive to radiotherapy and chemotherapy, systemic chemotherapy and local radiotherapy non-surgical treatment is the main treatment. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G16B20/20G16B25/20G16B40/10G16H50/20
CPCC12Q1/6886G16H50/20G16B20/20G16B40/10G16B25/20C12Q2600/112C12Q2600/156
Inventor 刘康刘鑫郝诗莹许雷张华马丹丹
Owner 深圳康华君泰生物科技有限公司
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