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Biomarkers for diagnosis of lung cancer

A biomarker and biological sample technology, applied in the field of markers to distinguish adenocarcinoma and squamous cell carcinoma, can solve the problem of complex malignant tumors

Pending Publication Date: 2020-01-07
THE NAT INST FOR BIOTECH IN THE NEGEV LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These can be detected by deep sequencing methods (Meldrum C et al. Clin Biochem Rev 2011;32:177-95), however it is complicated by the heterogeneity and complexity of malignancies (Marusyk A et al - Biochim Biophys Acta. 2010; 1805:105-17)

Method used

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  • Biomarkers for diagnosis of lung cancer
  • Biomarkers for diagnosis of lung cancer
  • Biomarkers for diagnosis of lung cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0249] Example 1: Mass Spectrometric Analysis of Protein Profiles from Healthy and Tumor Tissues from NSCLC Patients

[0250] To identify proteins showing altered expression levels in NSCLC tumor tissues relative to healthy tissues, 9 samples of cancerous and healthy tissues were collected from the same lungs of NSCLC patients and subjected to LC-HR MS / MS analysis. Hierarchical clustering based on the expression patterns of all detected proteins clearly allows the distinction between healthy and tumor tissues ( Figure 1A ), the expression levels of 1,494 proteins were altered (fold change (FC) ≥ |2| and false discovery rate (FDR) Figure 1B ). Up- and down-regulated proteins were further divided into two clusters based on the combination of FC and p-value, due to the "absence" of some proteins in some samples.

[0251] Next, functional analysis of differentially expressed proteins between cancerous and healthy lung tissue was performed using DAVID and the Gene Ontology data...

Embodiment 2

[0261] Example 2: Altered expression of metabolism-related and apoptosis-related proteins

[0262] Altered metabolism and the development of anti-apoptotic mechanisms are hallmarks of cancer. As previously described (WO2013 / 035095), several proteins associated with these features are overexpressed in certain types of cancer. Tumor and healthy tissue samples from the same lungs of NSCLC patients were analyzed by immunoblotting using specific antibodies to assess the levels of: voltage-dependent anion channel 1 (VDAC1), hexokinase I (HK-I), SMAC / Diablo (SMAC), apoptosis-inducing factor (AIF), mitochondrial antiviral signaling (MAVS), and Bcl-2 (Figure 2). Except for Bcl-2, all these proteins were significantly overexpressed (3-fold to 6-fold) in cancerous tissues compared to healthy tissues obtained from the same NSCLC patients ( Figure 2A , 2B ). LC-HR-MS / MS further confirmed that the expression levels of VDAC1, HK-I and SMAC were highly increased in cancer tissues ( ...

Embodiment 3

[0266] Example 3: Identification of biomarkers for lung cancer

[0267] LC-HR-MS / MS analysis data revealed many other proteins differentially expressed in NSCLC tumors (Table 6). The most significantly altered proteins expressed in tumors are presented in Table 6, together with their proposed functions and relationship to cancer. These include the Ras-related proteins Rab11B (Rab11B), HYOU1 (ORP150) and the heat shock protein HSPD1 (HSP60), the Ras-related protein Rab11B (Rab11B) is a member of the Ras superfamily of small GTP-binding proteins, HYOU1 (ORP150) in response to oxygen deprivation Plays a key role in the cellular mechanisms of cellular protection elicited. These findings were confirmed by immunoblot analysis, RNAseq UCSC XENA data, and qRT-PCR (Fig. 3).

[0268] Network analysis of the proteins identified here by proteomics (and determined by immunoblot analysis, RNAseq gene expression profiling data, and qRT-PCR) demonstrated that most of these proteins intera...

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Abstract

The present invention relates to biomarkers of lung cancer, particularly to markers that enable distinguishing between subtypes of non-small cell lung cancer (NSCLC), particularly between adenocarcinoma (AC) and squamous cell carcinoma (SCC). In particular, the present invention relates to means and methods for diagnosing, assessing the level of severity and selecting methods of treating NSCLC.

Description

[0001] field of invention [0002] The present invention relates to biomarkers of lung cancer, in particular markers capable of distinguishing subtypes of non-small cell lung cancer (NSCLC), especially adenocarcinoma (AC) and squamous cell carcinoma (SCC). In particular, the present invention relates to compositions and methods for diagnosing, assessing the level of severity of NSCLC and treating NSCLC. [0003] Background of the invention [0004] Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and represents the leading cause of cancer death in both men and women worldwide. Because most patients diagnosed with NSCLC are at an advanced stage of the disease, overall survival remains less than 12 months after standard treatment with platinum-based chemotherapy, radiation, and / or surgery. However, median overall survival can be increased by novel strategies implementing immunotherapy in different combinations or, if driver mutations are present, by t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C12Q1/6886G01N33/53G01N33/574A61K45/00A61P35/00
CPCC12Q1/6886A61P35/00G01N33/57423G01N2800/56G01N2800/60C12Q2600/158C12Q2600/112G01N33/6848G01N2560/00
Inventor 瓦尔达·肖尚-巴尔马茨
Owner THE NAT INST FOR BIOTECH IN THE NEGEV LTD
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