Micrornas expression signature for determination of tumors origin

Inactive Publication Date: 2010-10-28
ROSETTA GENOMICS +1
View PDF11 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0023]The invention further provides a method for identifying a gastrointestinal (GI) cancer, the method comprising: obtaining a biological sample from a subject; determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 1-5, a fragment t

Problems solved by technology

The differential diagnosis of hepatic lesions that include primary liver tumor and metastatic tumors is a frequent challenge in modern surgical pathology.
Identifying the origin of these tumors as well as differentiating liver metastases from primary hepatocellular carcinoma (HCC) is frequently required and poses a significant challenge that requires clinical-radiological correlation on top of careful pathological evaluation.
However, the primary site remains unknown in many patients, even on autopsy.
The appropriate management of such patients is unclear and there is a high variability in clinical approaches, accompanied by poor prognosis in most cases.
The pathological characterization of brain malignancies remains a diagnostic challenge.
Despite the advent of various high throughput genomic level technologies, which allow multiple DNA sequences, mRNAs or proteins to be evaluated simultaneously and systematically, these have had little impact on clinical procedures.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Micrornas expression signature for determination of tumors origin
  • Micrornas expression signature for determination of tumors origin
  • Micrornas expression signature for determination of tumors origin

Examples

Experimental program
Comparison scheme
Effect test

example 1

Specific microRNAs are Able to Distinguish Between Primary Non-Hepatic and Hepatic Tumors

[0205]microRNA expression levels were profiled in 144 tumor samples including 30 primary HCC samples, 63 primary tumors from epithelial origins, 46 liver metastases from epithelial origins, and 5 adenocarcinoma metastases to the liver from unknown origin. The primary HCC samples were compared to the other primary tumors and to the liver metastases samples. Hsa-miR-122a (SEQ ID NO: 32), which is a highly liver-specific microRNA, had the strongest effect when comparing primary HCC tumors to other primary tumors with a fold-change>90, and could identify HCC from other primary tumors (p-value=1.4e-38, AUC=1). However, this microRNA is also found at high levels in the RNA extracted from liver metastases (FIG. 1A), ostensibly due to contamination from the adjacent normal liver tissue, and is not a good marker for identifying liver metastases (fold-change of medians 1.1, p-value=0.28, AUC=0.56). By usi...

example 2

Specific microRNAs are Able to Distinguish Between Primary GI Tumors and Non-GI Primary Tumors

[0209]The microRNA expression can provide further information on the possible origin of liver metastases. Another pair of microRNAs, hsa-miR-194 (SEQ ID NO: 1) and hsa-miR-205 (SEQ ID NO: 4), had significant different expression (p-value<1e-12 for each) in primary tumors from gastrointestinal (GI) origin (14 colon, 5 pancreas, 5 stomach) compared to primary tumors of non-GI epithelial origin (24 lung, 15 breast). The ratio of these expression levels could be used to accurately identify primary tumors from non-GI origin: the decision rule “classify as non-GI primary when the expression of hsa-miR-205 is greater than half the expression of hsa-miR-194” (FIG. 2A; dashed line marks the decision boundary) had a sensitivity of 100% and specificity of 96% (AUC=0.9893). In the liver metastases, despite the small number of samples, this trend was maintained (FIG. 2B). However, since hsa-miR-194 is a...

example 3

Specific microRNAs are Able to Distinguish Between Primary Brain Tumors, Brain Metastases, Non-Brain Primary Tumors and Normal Brain Samples

[0210]microRNA expression levels were profiled on a microarray platform in 252 tumor samples including 15 brain primary tumor samples, 187 non-brain primary tumors, 50 brain metastases from various tissue origins and 2 normal brain samples. The brain primary tumor samples were compared to the other primary tumor samples, to normal brain samples and to samples of brain-located metastases (Table 6). Hsa-miR-124 (SEQ ID NO: 16), which is highly specific to the nervous system, displayed the greatest disparity in expression when comparing brain primary tumors to other primary tumors, with a fold-change of ˜100 (p-value=5.1e-57, AUC=0.9976, see Table 6). A combination of hsa-miR-124 and hsa-miR-219 (SEQ ID NO: 24) (B0, see methods) could be used to distinguish brain primary tumors from non-brain primary tumors with 100% accuracy (FIG. 4A). Other brain...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to view more

Abstract

The present invention provides a process for classification of specific cancers and tumors origin through the analysis of the expression patterns of specific microRNAs and nucleic acid molecules relating thereto. Classification according to a microRNA expression framework allows optimization of treatment, and determination of specific therapy.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]The present application is a Continuation-In-Part of Ser. No. 12 / 532,941, filed Sep. 24, 2009, which is the U.S. National Stage of PCT / IL2008 / 00396, filed Mar. 20, 2008, which claims priority to U.S. Provisional applications 60 / 907,266, filed Mar. 27, 2007, 60 / 929,244, filed Jun. 19, 2007, and 61 / 024,565, filed Jan. 30, 2008. The present application is also a Continuation-In Part of PCT / IL2008 / 001525, filed Nov. 20, 2008, which claims priority to U.S. Provisional Application Nos. 60 / 989,458, filed Nov. 21, 2008, 61 / 043,407, filed Apr. 9, 2008, and 61 / 073,774, filed Jun. 19, 2008. All of the priority applications are herein incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to methods for classification of cancers and tumors origin. Specifically the invention relates to microRNA molecules associated with specific cancer, as well as various nucleic acid molecules relating thereto or derived...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C12Q1/68
CPCC12Q1/6886C12Q2600/178C12Q2600/112C12Q2600/158
Inventor ROSENFELD, NITZANROSENWALD, SHAIBARSHACK, IRISNASS, DVORA
Owner ROSETTA GENOMICS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap