Method for determining the survival prognosis of a patient suffering from pancreatic cancer
AssigneeAcobiom
InventorDavid Piquemal
Life of this patent
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Abstract
The present invention relates to pancreatic cancer, and more particularly to the survival prognosis of a patient suffering from pancreatic cancer. The invention also aims to determine the suitability of said patient to receive a treatment for pancreatic cancer, in particular a treatment with gemcitabine. The invention also concerns a method for monitoring the effectiveness of a treatment for pancreatic cancer, and advantageously a treatment with gemcitabine, by implementing the method.
Claims12
A method for treating a patient suffering from pancreatic cancer, comprising the following steps:
- a) measuring the level of expression of each gene (Ctgene) of a combination of at least NME4 and ARL4C marker genes and optionally ITPR3, SESN3, and/or RPLP1 marker gene(s) and the level of expression of two ubiquitous B2M and GAPDH genes in a blood sample taken previously from said patient, said levels of expression being measured from the transcription level of the RNA or cDNA of said gene as number of cycle(s) (Ct, “cycle threshold”) by real-time quantitative PCR (qPCR), the level of expression of the marker genes then being normalized with respect to the level of expression of the two ubiquitous genes according to ΔCtgene=Ctgene−[(mean value of the) Ct (ubiquitous genes)] to obtain a normalized level of expression ΔCtgene for each marker gene the level of expression of which has been measured;
- b) comparing the level of expression measured for the marker genes in step a) in said patient against a reference threshold, and for each gene the expression of which has been measured:
- i) determining a value INDEXgene, which is dependent on the normalized level of expression of the gene, defined by:
- INDEXgene=+1*β coefficient of the gene, if ΔCtgene>reference threshold of the gene, and
- INDEXgene=−1*β coefficient of the gene, if ΔCtgene<reference threshold of the gene, and
- in which the β coefficient and the reference threshold (Sref) of a given gene are as defined below
- Gene
- Sref
- β coefficient
- NME4
- 3.1864
- −1.3207
- ITPR3
- 6.4014
- 1.0850
- SESN3
- 3.6262
- 1.0301
- ARL4C
- 2.6286
- 1.3577
- RPLP1
- 6.3748
- 1.0101
- ii) determining for a given patient a value INDEXpatient equal to the sum of the INDEXgene of the genes of the combination, and
- iii) comparing INDEXpatient against a final reference threshold previously determined for the combination of genes;
- and
- c) administering gemcitabine to the patient if the INDEXpatient for the combination of genes is determined to be less than the value of the final reference threshold for the combination of genes, or
- administering FOLFIRINOX or erlotinib to the patient if the INDEXpatient for the combination of genes is determined to be greater than the value of the final reference threshold for the combination of genes.
A method for treating pancreatic cancer, comprising administering gemcitabine to a patient suffering from pancreatic cancer at time intervals, and during the interval between treatment with gemcitabine, monitoring the efficacy of treatment by:
- a) measuring the level of expression of each gene (Ctgene) of a combination of at least NME4 and ARL4C marker genes and optionally ITPR3, SESN3 and/or RPLP1 marker gene(s), and the level of expression of two ubiquitous B2M and GAPDH genes in a blood sample taken from said patient, said levels of expression being measured from the transcription level of the RNA or cDNA of said gene as number of cycle(s) (Ct, “cycle threshold”) by real-time quantitative PCR (qPCR), the level of expression of the marker genes then being normalized with respect to the level of expression of the two ubiquitous genes according to ΔCtgene=Ctgene−[(mean value of the) Ct (ubiquitous genes)] to obtain a normalized level of expression ΔCtgene for each marker gene the level of expression of which has been measured;
- b) comparing the level of expression measured for the marker genes in step a) in said patient against a reference threshold, and for each gene the expression of which has been measured:
- i) determining a value INDEXgene, which is dependent on the normalized level of expression of the gene, defined by:
- INDEXgene=+1*β coefficient of the gene, if ΔCtgene>reference threshold of the gene, and
- INDEXgene=−1*β coefficient of the gene, if ΔCtgene<reference threshold of the gene,
- in which the β coefficient and the reference threshold (Sref) of a given gene are as defined below
- Gene
- Sref
- β coefficient
- NME4
- 3.1864
- −1.3207
- ITPR3
- 6.4014
- 1.0850
- SESN3
- 3.6262
- 1.0301
- ARL4C
- 2.6286
- 1.3577
- RPLP1
- 6.3748
- 1.0101
- ii) determining for a given patient a value INDEXpatient equal to the sum of the INDEXgene of the genes of the combination, and
- iii) comparing the INDEXpatient against a final reference threshold previously determined for the combination of genes;
- and
- c) proceeding with administering gemcitabine to the patient to continue treatment with gemcitabine at time intervals if the INDEXpatient for the combination of genes is determined to be less than the value of the final reference threshold for the combination of genes, or
- changing to a non-gemcitabine-based treatment by administering FOLFIRINOX or erlotinib to the patient if the INDEXpatient for the combination of genes is determined to be greater than the value of the final reference threshold for the combination of genes.
Dependencies are inferred from the claim text.