Determining cancer agressiveness, prognosis and responsiveness to treatment

An invasive, cancer-based technology for specific peptides, chemical instruments and methods, biochemical equipment and methods, etc.

Inactive Publication Date: 2017-05-10
COUNCIL OF THE QUEENSLAND INST OF MEDICAL RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, such an approach is at an early stage, and considerable work is required to deve

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  • Determining cancer agressiveness, prognosis and responsiveness to treatment
  • Determining cancer agressiveness, prognosis and responsiveness to treatment
  • Determining cancer agressiveness, prognosis and responsiveness to treatment

Examples

Experimental program
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Effect test

Embodiment 1

[0386] Materials and methods

[0387] Meta-analysis of global gene expression in TNBC

[0388] In Oncomine TM database 19 (Compendia Bioscience, MI) using breast cancer primary filter (130 datasets), sample filter to use clinical specimens and dataset filter to use mRNA dataset with more than 151 patients (22 datasets) , we performed a global gene expression meta-analysis. Patients of all ages, sexes, disease stages, or treatments were included. Three additional filters were applied for three independent differential analyses: (1) triple negative (TNBC cases vs non-TNBC cases, 8 data sets 49-56 ); (2) Metastasis event analysis at 5 years (transfer event vs non-transfer event, 7 data sets 53,54,57-61 ) and (3) survival at 5 years (patients who died vs. patients who survived, 7 datasets 49,54,56,58,61-63 ). Dysregulated genes were selected based on the median p-value of the median gene rank in overexpression pattern or underexpression pattern in the dataset ( Figure 8 )...

Embodiment 2

[0545] Materials and methods

[0546] Meta-analysis of global gene expression in TNBC

[0547] In Oncomine TM Database [37] (Compendia Bioscience, Ann Arbor, MI) using primary filter for breast cancer (130 datasets), sample filter to use clinical specimens and dataset filter to use mRNA data with more than 151 patients set (22 datasets), we performed a meta-analysis of global gene expression. Two additional filters were used to perform two independent differential analyses. The first differential analysis was an analysis of metastatic events at 5 years (metastatic events vs. patients, 7 datasets [39, 57, 59, 61-64]). For each of the two differential analyses, dysregulated genes were selected based on the median p-value of the median gene rank for either the overexpression pattern or the underexpression pattern in the dataset.

[0548] Export 28-imprint (TN imprint)

[0549] The online tool KM-Plotter [38], which collates gene expression data of more than 4000 breast canc...

Embodiment 3

[0751] The iBCR test presented herein was developed from a meta-analysis of gene expression profiles of breast cancer. The test is based on the expression of 43 genes that are predictive as signatures in breast cancer (regardless of subtype). The test was also found to be predictive in lung adenocarcinoma. Patients with high iBCR scores had much worse overall survival than those with low iBCR scores.

[0752] In the current study, the Cancer Genome Atlas (TCGA) dataset was investigated for multiple cancer types for three purposes. First, to determine the differences at the protein level between breast cancer cases with high iBCR scores and breast cancer cases with low iBCR scores. This comparison was also performed for lung adenocarcinoma. Second, to determine whether dysregulated proteins / phosphoproteins between high and low iBCR score tumors are predictive. Finally, the prognostic value of iBCR miRNA signature and associated protein signature was predictive in other canc...

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Abstract

The invention provides methods of determining the aggressiveness, prognosis and response to therapy for particular cancers, which include comparing the expression levels of one or a plurality of differentially expressed genes from one or more 5 functional metagenes, including a carbohydrate/lipid metabolism metagene, a cell signalling metagene, a cellular development metagene, a cellular growth metagene, a chromosome segregation metagene, a DNA replication/recombination metagene, an immune system metagene, a metabolic disease metagene, a nucleic acid metabolism metagene, a post-translational modification metagene, a protein 10 synthesis/modification metagene and a multiple networks metagene. The method disclosed herein may be particularly suitable as a companion diagnostic for cancer therapies.

Description

technical field [0001] The present invention relates to cancer. More particularly, the present invention relates to methods of determining the aggressiveness of cancer, cancer prognosis and / or predicting response to anticancer treatments. Background technique [0002] Hormone receptors (ER and PR) and HER2 are standard biomarkers used in clinical practice to aid in histopathological typing of breast cancer and to make control decisions. Hormone receptor (HR)- and HER2-positive tumors benefit from tamoxifen and anti-HER2 therapy, respectively. On the other hand, there is currently no targeted drug therapy for the control of triple-negative breast cancer (TNBC, which lacks expression of HR / HER2). TNBC is more sensitive to chemotherapy than HR-positive tumors because it is usually more proliferative and pathological complete response (pCR) after chemotherapy is more likely in TNBC than in non-TNBC 1,2 . Paradoxically, TNBC is associated with poorer survival compared with no...

Claims

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Application Information

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IPC IPC(8): C12Q1/68
CPCC12Q2600/112C12Q2600/118C12Q2600/158C12Q1/6886A61P35/00C12Q2600/136C07K16/2818C07K16/2887C07K2317/24G01N33/57415
Inventor F·亚尔-埃杰
Owner COUNCIL OF THE QUEENSLAND INST OF MEDICAL RES
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