US2015176080A1PendingUtilityA1
Method of hepatocellular carninoma classification and prognosis
Est. expiryNov 30, 2025(expired)· nominal 20-yr term from priority
G01N 33/57557G01N 33/57407C12Q 2600/112C12Q 1/6886G16B 40/30G16B 40/20G16B 25/10G16B 40/10G16B 40/00C12Q 2600/106G16B 25/00C12Q 2600/136C12Q 2600/118C12Q 2600/154
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Claims
Abstract
Methodology for the in vitro classification and/or prognosis of hepatocellular carcinoma (HCC) from a HCC sample is based on the determination of the expression profile of particular gene combinations. For example, in one embodiment, a method comprises measuring the expression level in an HCC sample of at least 8 genes selected from the group consisting of: RAB1A, REG3A, NRAS, RAMP3, MERTK, PIR, EPHA1, LAMA3, G0S2, HN1, PAK2, AFP, CYP2C9, CDH2, HAMP, SAE1, ADH6, DCN, FLJ10159, ALDH1L1, IGF1, LECT2, SLC38A1, SPARCL1, CTNNA2, GLUL, LEF1, MATN2, MME, PFN2, SPINT2, TBX3, and FGFR2; b) calculating 6 subgroup distances from the expression profile; and c) classifying the HCC tumor in the subgroup for which the subgroup distance is the lowest, wherein the 6 subgroups G1, G2, G3, G4, G5, and G6 are defined by the presence (+) or absence (−) of their clinical and genetic features.
Claims
exact text as granted — not AI-modified1 .- 25 . (canceled)
26 . A method of in vitro prognosis of global survival and/or survival without relapse of a subject suffering from HCC, comprising:
a) Providing a liver HCC sample of said subject suffering from HCC and extracting proteins or mRNA from the HCC sample; b) measuring in vitro the expression levels of a genes combination comprising TAF9 and at least one gene selected from the group consisting of NRCAM, PIR, RAMP3, SLC21A2, TNA, HN1, PSMD1, MRPS7, CDC20, ENO1, HLF, STRA13, RAGD, NRAS, ARFGEF2, RAB1A, G0S2, SMAD3, DNAJA3, HELO1, RHOQ, C14orf156, NPEPPS, PDCD2, PHB, KIAA0090, IMP-3, KPNA2, KIAA0268, UNQ6077, LOC440751, G6PD, STK6, TFRC, GLA, TRIP13, SPP1, AKR1C1, AKR1C2, GIMAP5, ADM, CCNB1, TKT, AGPS, RAN, NUDT9, HRASLS3, HLA-DQA1, NEU1, RARRES2, PAPOLA, ABCB6, BIRC5, FLJ20273, C14orf109, CHKA, TUBB2, HMGB3, TXNRD1, IFITM1, KIAA0992, MPPE1, KLRB1, CCL5, SYNE1, DNASE1L3, CYP2C18, PACSIN2, PON3, and PPP2R1B; c) calculating from said expression levels a global survival score and/or a survival without relapse score; and d) comparing the obtained global survival score and/or survival without relapse score each with a threshold value, wherein
a global survival/survival without relapse score strictly inferior to said threshold value indicates a good survival/survival without relapse prognosis, whereas
a global survival/survival without relapse score superior or equal to said threshold value indicates a bad survival/survival without relapse prognosis.
27 . The method of claim 26 , wherein the genes combination comprises TAF9 and at least one gene selected from the group consisting of NRCAM, PIR, RAMP3, SLC21A2, TNA, HN1, PSMD1, MRPS7, CDC20, ENO1, HLF, STRA13, RAGD, NRAS, ARFGEF2, RAB1A, G0S2, SMAD3, DNAJA3, HELO1, and RHOQ.
28 . The method of claim 26 , wherein global survival is prognosed and the genes combination is:
TAF9, PIR, NRCAM, and RAMP3, TAF9, NRCAM, SLC21A2, and PSMD1, TAF9, NRCAM, RAMP3, and PSMD1, TAF9, NRCAM, NRAS, RAMP3, and PSMD1, or TAF9, NRCAM, RAMP3, PSMD1 and ARFGEF2.
29 . The method of claim 28 , wherein the genes combination consists of TAF9, NRCAM, RAMP3, PSMD1 and ARFGEF2.
30 . The method of claim 26 , wherein survival without relapse is prognosed and the genes combination is:
TAF9, and G0S2, TAF9, NRCAM, and RAMP3, TAF9, G0S2, and RAMP3, TAF9, NRCAM, DNAJA3, and RAMP3, or TAF9, NRCAM, G0S2, DNAJA3, and RAMP3.
31 . The method of claim 30 , wherein the genes combination consists of TAF9, NRCAM, and RAMP3.
32 . The method of claim 26 , wherein the expression levels are determined at the nucleic level.
33 . The method of claim 32 , wherein the expression levels are determined using quantitative PCR.
34 . The method of claim 33 , wherein the genes combination consists of TAF9, NRCAM, RAMP3, PSMD1 and ARFGEF2, and the following formula is used:
Global
survival
score
(
sample
i
)
=
∑
t
=
1
…
n
β
(
gene
t
)
·
(
2
-
Δ
Ct
(
sample
i
,
gene
t
)
-
μ
(
gene
t
)
)
,
wherein
n represents the number of genes in the combination,
t represents the number of each gene in the combination displayed below, and
the value of each β(gene t ) and μ(gene t ) coefficients is in an interval of 10% around those displayed below
Gene number
Gene symbol
μ
β
1
TAF9
7.28
0.129
2
NRCAM
1.59
0.252
3
RAMP3
0.14
−6.133
4
PSMD1
4.66
0.024
5
ARFGEF2
3.66
−0.025
35 . The method of claim 34 , wherein the threshold value used for the prognosis is in an interval of 10% around −0.393.
36 . The method of claim 33 , wherein the genes combination consists of TAF9, NRCAM, and RAMP3, and the following formula is used:
Survival
without
relapse
score
(
sample
i
)
=
∑
t
=
1
…
n
β
(
gene
t
)
·
(
2
-
Δ
Ct
(
sample
i
,
gene
t
)
-
μ
(
gene
t
)
)
wherein
n represents the number of genes in the combination,
t represents the number of each gene in the combination displayed below, and
the value of each β(gene t ) and μ(gene t ) coefficients is in an interval of 10% around those displayed below
Gene number
Gene symbol
μ
β
1
TAF9
7.28
0.127
2
NRCAM
1.59
0.196
3
RAMP3
0.14
−3.886
37 . The method of claim 36 , wherein the threshold value used for the prognosis is in an interval of 10% around −0.461.
38 . The method of claim 26 , wherein the liver HCC sample is a liver HCC biopsy or a HCC tumor surgical resection.
39 . A method of treatment of a subject suffering from HCC, comprising:
a) prognosing global survival and/or survival without relapse of said subject according to the method of claim 26 , and b) administering to said subject an adjuvant therapy in the presence of a bad prognosis, while not administering such an adjuvant therapy in the absence of a bad prognosis.
40 . The method of claim 39 , wherein said adjuvant therapy is selected from chemotherapy and radiotherapy.
41 . A kit for the in vitro prognosis of global survival and/or survival without relapse from a liver HCC sample of a subject suffering from HCC, comprising reagents for the determination of an expression profile comprising a combination of TAF9 at least one gene selected from the group consisting of NRCAM, PIR, RAMP3, SLC21A2, TNA, HN1, PSMD1, MRPS7, CDC20, ENO1, HLF, STRA13, RAGD, NRAS, ARFGEF2, RAB1A, G0S2, SMAD3, DNAJA3, HELO1, RHOQ, C14orf156, NPEPPS, PDCD2, PHB, KIAA0090, IMP-3, KPNA2, KIAA0268, UNQ6077, LOC440751, G6PD, STK6, TFRC, GLA, TRIP13, SPP1, AKR1C1, AKR1C2, GIMAP5, ADM, CCNB1, TKT, AGPS, RAN, NUDT9, HRASLS3, HLA-DQA1, NEU1, RARRES2, PAPOLA, ABCB6, BIRC5, FLJ20273, C14orf109, CHKA, TUBB2, HMGB3, TXNRD1, IFITM1, KIAA0992, MPPE1, KLRB1, CCL5, SYNE1, DNASE1L3, CYP2C18, PACSIN2, PON3, and PPP2R1B.Join the waitlist — get patent alerts
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