# US 11,306,362 B2 · Gene signature predictive of hepatocellular carcinoma response to transcatheter arterial chemoembolization (TACE) > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,362 B2 - Document ID: US11306362B2 - Status: Granted - Kind: B2 - Application number: 16/076,239 - Filed: 2017-02-07 - Published: 2020-01-30 - Granted: 2022-04-19 - Earliest claimed: 2016-02-08 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services - Applicants: The U.S.A., as represented by the Secretary, Department of Health and Human Services - Inventors: Xin Wei Wang; Valerie Fako Miller - Web page: https://patentgrep.com/patent/US11306362B2 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/112: Disease subtyping, staging or classification - C12Q 2600/158: Expression markers - C12Q 2600/16: Primer sets for multiplex assays - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## 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. ## Claims ### Claim 1 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. ### Claim 2 (depends on 1) The method of claim 1, further comprising detecting a decrease in expression of GABA(A) receptors associated protein like 3, pseudogene (GABARAPL3) in an HCC sample obtained from a subject diagnosed with HCC, relative to a control. ### Claim 3 (depends on 1) The method of claim 1, further comprising detecting expression of 1 to 10 housekeeping genes or proteins. ### Claim 4 (depends on 1) The method of claim 1, wherein the subject diagnosed with HCC has a chronic viral infection or cirrhosis of the liver. ### Claim 5 (depends on 1) The method of claim 1, wherein detecting an increase or decrease in gene expression comprises detecting a level of ASNS, CDK1, DNASE1L3, FBXL5, GOT2, GRHPR, IARS, LGALS3, LHFPL2, MFGE8, MKI67, PEBP1, TNFSF10, and UBB mRNA using a microscope device. ### Claim 6 (depends on 5) The method of claim 5, further comprising detecting a level of GABARAPL3 mRNA using a microscope device. ### Claim 7 (depends on 1) The method of claim 1, further comprising converting gene expression values to a z-score and administering transarterial chemoembolization (TACE) to the subject. ### Claim 8 (depends on 7) The method of claim 7, further comprising applying a prognostic index equation to predict whether the HCC will respond to TACE. ### Claim 9 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. ### Claim 10 (depends on 9) The method of claim 9, further comprising detecting a decrease in expression of GABA(A) receptors associated protein like 3, pseudogene (GABARAPL3) in an HCC sample obtained from a subject diagnosed with HCC, relative to a control. ### Claim 11 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. ### Claim 12 (depends on 11) The method of claim 11, further comprising detecting a decrease in expression of GABA(A) receptors associated protein like 3, pseudogene (GABARAPL3) relative to a control. ### Claim 13 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. ### Claim 14 (depends on 13) The method of claim 13, wherein the TACE comprises one or more of cisplatin, adriamycin, mitomycin, and doxorubicin. ### Claim 15 (depends on 13) The method of claim 13, further comprising measuring alphafetoprotein (AFP) in a blood sample from the subject. ### Claim 16 (depends on 1) The method of claim 1, further comprising detecting expression of 1 to 6 housekeeping genes or proteins. ### Claim 17 (depends on 9) The method of claim 9, wherein the subject diagnosed with HCC has a chronic viral infection or cirrhosis of the liver. ### Claim 18 (depends on 11) The method of claim 11, wherein the subject diagnosed with HCC has a chronic viral infection or cirrhosis of the liver. ### Claim 19 (depends on 13) The method of claim 13, wherein the subject diagnosed with HCC has a chronic viral infection or cirrhosis of the liver.