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US 11,306,362 B2Granted
Gene signature predictive of hepatocellular carcinoma response to transcatheter arterial chemoembolization (TACE)
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsXin Wei Wang, Valerie Fako Miller
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Abstract
This disclosure provides methods for predicting the likelihood that a hepatocellular carcinoma (HCC) will respond to transcatheter arterial chemoembolization (TACE) using a gene signature of 14 or 15 genes. Also provided are nucleic acid probes and kits for detecting the gene signature.
Claims19
A method of detecting expression of a plurality of genes, comprising:
- detecting an increase in expression of asparagine synthetase (ASNS), cyclin-dependent kinase 1 (CDK1), F-box and leucine-rich repeat protein 5 (FBXL5), isoleucyl-tRNA synthetase (TARS), lectin, galactoside-binding, soluble 3 (LGALS3), lipoma HMGIC fusion partner-like 2 protein (LHFPL2), antigen Ki-67 (MKI67), and ubiquitin B (UBB) and a decrease in expression of deoxyribonuclease I-like 3 (DNASE1L3), glutamic-oxaloacetic transaminase 2, mitochondrial (GOT2), glyoxylate-reductase/hydroxypyruvate reductase (GRHPR), milk fat globule-EGF factor 8 protein (MFGE8), phosphatidylethanolamine binding protein 1 (PEBP1), and tumor necrosis factor superfamily, member 10 (TNFSF10), in a hepatocellular carcinoma (HCC) sample obtained from a subject diagnosed with HCC, relative to a control.
A method of detecting expression of a plurality of genes, comprising:
- detecting an increase in expression of asparagine synthetase (ASNS), cyclin-dependent kinase 1 (CDK1), F-box and leucine-rich repeat protein 5 (FBXL5), isoleucyl-tRNA synthetase (TARS), lectin, galactoside-binding, soluble 3 (LGALS3), lipoma HMGIC fusion partner-like 2 protein (LHFPL2), antigen Ki-67 (MKI67), and ubiquitin B (UBB) and a decrease in expression of deoxyribonuclease I-like 3 (DNASE1L3), glutamic-oxaloacetic transaminase 2, mitochondrial (GOT2), glyoxylate-reductase/hydroxypyruvate reductase (GRHPR), milk fat globule-EGF factor 8 protein (MFGE8), phosphatidylethanolamine binding protein 1 (PEBP1), and tumor necrosis factor superfamily, member 10 (TNFSF10), in a hepatocellular carcinoma (HCC) sample obtained from a subject diagnosed with HCC, relative to a control using a probe set comprising a nucleic acid probe specific for each of ASNS, CDK1, DNASE1L3, FBXL5, GOT2, GRHPR, IARS, LGALS3, LHFPL2, MFGE8, MKI67, PEBP1, TNFSF10, and UBB.
A method of treating a hepatocellular carcinoma (HCC) in a subject, comprising:
- determining that the HCC will respond to transarterial chemoembolization (TACE) by detecting an increase in expression of asparagine synthetase (ASNS), cyclin-dependent kinase 1 (CDK1), F-box and leucine-rich repeat protein 5 (FBXL5), isoleucyl-tRNA synthetase (TARS), lectin, galactoside-binding, soluble 3 (LGALS3), lipoma HMGIC fusion partner-like 2 protein (LHFPL2), antigen Ki-67 (MKI67), and ubiquitin B (UBB) and a decrease in expression of deoxyribonuclease I-like 3 (DNASE1L3), glutamic-oxaloacetic transaminase 2, mitochondrial (GOT2), glyoxylate-reductase/hydroxypyruvate reductase (GRHPR), milk fat globule-EGF factor 8 protein (MFGE8), phosphatidylethanolamine binding protein 1 (PEBP1), and tumor necrosis factor superfamily, member 10 (TNFSF10), relative to a control;
- and
- administering TACE to the subject.
A method of treating hepatocellular carcinoma (HCC), comprising:
- measuring increased expression of asparagine synthetase (ASNS), cyclin-dependent kinase 1 (CDK1), F-box and leucine-rich repeat protein 5 (FBXL5), isoleucyl-tRNA synthetase (TARS), lectin, galactoside-binding, soluble 3 (LGALS3), lipoma HMGIC fusion partner-like 2 protein (LHFPL2), antigen Ki-67 (MKI67), and ubiquitin B (UBB) in an HCC sample from a subject relative to a control;
- measuring decreased expression of deoxyribonuclease I-like 3 (DNASE1L3), glutamic-oxaloacetic transaminase 2, mitochondrial (GOT2), glyoxylate-reductase/hydroxypyruvate reductase (GRHPR), milk fat globule-EGF factor 8 protein (MFGE8), phosphatidylethanolamine binding protein 1 (PEBP1), and tumor necrosis factor superfamily, member 10 (TNFSF10) in an HCC sample from a subject relative to a control;
- and
- treating the subject with transarterial chemoembolization (TACE), thereby treating the HCC.
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Dependencies are inferred from the claim text.