EP2872645A1 - Méthode et trousse permettant de prédire ou de surveiller la réaction d'un patient cancéreux à la chimiothérapie, à partir de la mesure du niveau d'expression du gène tmem45a - Google Patents

Méthode et trousse permettant de prédire ou de surveiller la réaction d'un patient cancéreux à la chimiothérapie, à partir de la mesure du niveau d'expression du gène tmem45a

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Publication number
EP2872645A1
EP2872645A1 EP13727840.4A EP13727840A EP2872645A1 EP 2872645 A1 EP2872645 A1 EP 2872645A1 EP 13727840 A EP13727840 A EP 13727840A EP 2872645 A1 EP2872645 A1 EP 2872645A1
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EP
European Patent Office
Prior art keywords
cancer
tmem45a
gene
sample
measuring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
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EP13727840.4A
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German (de)
English (en)
Inventor
Carine Michiels
Lionel FLAMANT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Universite de Namur
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Universite de Namur
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Application filed by Universite de Namur filed Critical Universite de Namur
Priority to EP13727840.4A priority Critical patent/EP2872645A1/fr
Publication of EP2872645A1 publication Critical patent/EP2872645A1/fr
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the present invention is in the field of cancer diagnostic in relation to TMEM45A expression, and of associated treatments.
  • efflux pump such as the P-glycoprotein encoded by the MDR1 gene or proteins from ABC (ATP-binding cassette) transporter family, which expulses the chemotherapeutic drug out of the tumor cells represents a paradigm of therapy resistance.
  • hypoxia can either promote apoptosis and cell death or contrariwise induce cell growth and survival by provoking an adaptive response.
  • tumor hypoxia has been associated with resistance to chemotherapy and radiotherapy, with tumor progression, aggressiveness and metastasis, and therefore with an increased probability of tumor recurrence.
  • TMEM45A protein The function of TMEM45A protein is almost unknown, and nothing is known about its cellular localization .
  • TMEM45A was found upregulated in hypoxia in umbilical cord blood CD133+ cells.
  • a first aspect of the present invention is a method for predicting the response of a human patient (suffering of a cancer) to a chemotherapy treatment (such as Taxol or etoposide) against this cancer, (this method) comprising the step of measuring the expression level of TMEM45A gene in a sample (e.g. a tumor sample) consisting essentially of cancer cells obtained from this human patient suffering of cancer.
  • a chemotherapy treatment such as Taxol or etoposide
  • a related aspect of the present invention is a method for monitoring the response of a human patient (suffering of cancer) to a chemotherapy (such as Taxol or etoposide) treatment against this cancer, (this method) comprising the step of measuring the expression level of TMEM45A gene in a sample (e.g. a tumor sample) consisting essentially of cancer cells obtained from this human patient suffering of cancer.
  • a chemotherapy such as Taxol or etoposide
  • Another related aspect of the present invention is a method for prognosticating the outcome of a cancer in a human patient comprising the step of measuring the expression level of TMEM45A gene in a sample (e.g. a tumor sample) consisting essentially of cancer cells obtained from this human patient suffering of cancer.
  • a sample e.g. a tumor sample
  • the cancer is a solid tumor cancer, more preferably selected from the group consisting of breast cancer, lung cancer, colon cancer, head and neck cancer, pancreas cancer, liver cancer, kidney cancer, brain cancer, thyroid cancer, ovarian cancer, sarcoma and melanoma, being more still preferably breast cancer, head and neck cancer, lung cancer or kidney cancer.
  • these methods further comprise the step of measuring the expression level of TMEM45A gene in a non-cancer sample consisting of the original and/or native non-cancer cells and possibly the step of comparing the expression level in the cancer cells and in the non cancer cells, possibly wherein this non cancer sample is obtained from the human patient suffering of cancer.
  • a high expression level of TMEM45A gene corresponds to a ratio of TMEM45A gene expression in the cancer sample being of at least 2-fold, preferably at least 3-fold or even at least 10-fold higher than in the non- cancer sample.
  • Such a high expression level represents a worse prognosis and/or a resistance towards chemotherapeutic agents (such as Taxol or etoposide) .
  • the chemotherapy treatment is Paclitaxel (Taxol) or etoposide.
  • these methods further comprise the step of measuring the expression level of at least another (1, 2, 3, 4, 5 or even all the) gene(s) selected from Table 1, preferably at least SPAG4 gene, in the sample consisting essentially of cancer cells, and possibly also in the sample consisting of the original and/or native non-cancer cells .
  • Another related aspect of the present invention is a diagnostic kit comprising tools for measuring the expression of TMEM45A gene.
  • this kit comprises tools for measuring the expression level of less than 100 other genes than TMEM45A gene.
  • this kit further comprises tools for measuring the expression level of at least another (1, 2, 3, 4, 5 or even all the) gene(s) selected from Table 1, preferably at least SPAG4 gene.
  • this kit consists essentially of tools for measuring the expression of TMEM45A gene (and possibly of gene(s) from Table 1) .
  • kits of the present invention for prognosticating the outcome of a cancer in a human patient, or for predicting the response to a chemotherapy treatment of a cancer in a human patient, and/or for monitoring the response to a chemotherapy treatment of a cancer in a human patient.
  • This use is preferably applied on (genes and/or mRNA and/or proteins isolated from) a solid tumor cancer, preferably selected from the group consisting of breast cancer, lung cancer, colon cancer, pancreas cancer, head and neck cancer, liver cancer, kidney cancer, brain cancer, thyroid cancer, ovarian cancer, sarcoma and melanoma, being more preferably breast cancer, lung cancer, head and neck cancer or kidney cancer.
  • a solid tumor cancer preferably selected from the group consisting of breast cancer, lung cancer, colon cancer, pancreas cancer, head and neck cancer, liver cancer, kidney cancer, brain cancer, thyroid cancer, ovarian cancer, sarcoma and melanoma, being more preferably breast cancer, lung cancer, head and neck cancer or kidney cancer.
  • Another related aspect of the present invention is chemotherapy (such as Taxol or etoposide) for use in a human patient suffering of a cancer, wherein TMEM45A gene expression in a cancer sample is less than 2- fold higher than in original and/or native non-cancer sample .
  • the preferred chemotherapy treatment are selected from the group consisting of Paclitaxel (taxol) and etoposide.
  • anthracyclines and also mitomycin C or camptothecin
  • TMEM45A can be used in patients having a high expression (a ratio of expression of more than 2- fold, preferably more than 3-fold) level of TMEM45A.
  • These chemotherapy treatments are preferably used for the treatment of solid tumor cancers, preferably selected from the group consisting of breast cancer, lung cancer, colon cancer, pancreas cancer, liver cancer, kidney cancer, brain cancer, thyroid cancer, ovarian cancer, sarcoma and melanoma, being more preferably breast cancer, lung cancer or kidney cancer.
  • Another related aspect of the present invention is an anti TMEM45A for use in the treatment of a solid tumor cancer affecting a patient, preferably in combination with another chemo therapeutic drug (such as Taxol or etoposide) .
  • another chemo therapeutic drug such as Taxol or etoposide
  • TMEM45A silencing on the protective effect of hypoxia on paclitaxel-induced apoptosis.
  • TMEM45A siRNA siRNA; SEQ. ID. O: 4-6
  • RISC-free control siRNA RF
  • 50nM, 24h MDA-MB-231 cells were incubated under normoxic (N) or hypoxic (H) conditions with or without paclitaxel (tax, 50 ⁇ ) or epirubicin (epi, ⁇ ) for 16 hours.
  • caspase 3 activity was assayed by measuring free AFC released from the cleavage of the caspase 3 specific substrate Ac-DEVD-AFC.
  • TMEM45A for instance NCBI ref seq: NM_018004; SEQ.ID.NO:l
  • NM_018004 for instance NCBI ref seq: NM_018004; SEQ.ID.NO:l
  • TMEM45A for instance NCBI ref seq: NM_018004; SEQ.ID.NO:l
  • TMEM45A gene overexpression was shown to be triggered by hypoxia but can be reduced (in this context) by several drugs, such as anthracyclins (and also mitomycin C or camptothecin) .
  • TMEM45A gives a clue on how a (human) patient suffering of cancer will react to treatments such as to chemotherapeutic drugs (including Taxol or etoposide) .
  • chemotherapeutic such as Taxol or etoposide
  • a first aspect of the present invention is a
  • (diagnostic) method for predicting the response of a (human) patient suffering of a cancer to a chemotherapy treatment such as Paclitaxel (Taxol) or etoposide
  • a chemotherapy treatment such as Paclitaxel (Taxol) or etoposide
  • TMEM45A gene and/or of other genes from Table 1
  • the cancer (to be analyzed in the methods of the present invention) is a solid tumor cancer.
  • the sample (to be analyzed in the methods of the present invention) comprising (consisting essentially of, or consisting of) cancer cells is a tumor sample (e.g. a biopsy) obtained from this solid tumor cancer.
  • solid tumor cancer refers to as a cancer selected from the group consisting of breast cancer, lung cancer, head and neck cancer, colon cancer, pancreas cancer, liver cancer, kidney cancer, brain cancer, thyroid cancer, ovarian cancer, sarcoma and melanoma, being preferably breast cancer, lung cancer, head and neck cancer or kidney cancer .
  • a related aspect of the present invention is a method for monitoring the response of a (human) patient suffering of cancer to a chemotherapy treatment (such as Paclitaxel (Taxol) or etoposide) of this cancer, which comprises the step of measuring the expression level of TMEM45A gene (and/or of other genes from Table 1) in a sample comprising (consisting essentially of, or consisting of) cancer cells.
  • a chemotherapy treatment such as Paclitaxel (Taxol) or etoposide
  • Another related aspect of the present invention is a method for prognosticating the outcome of a cancer in a (human) patient, which comprises the step of measuring the expression level of TMEM45A gene (and/or of other genes from Table 1) in a sample comprising (consisting essentially of, or consisting of) cancer cells.
  • the methods of the present invention further comprise the step of measuring the (relative; e.g. after normalization with housekeeping gene (s) ) expression level of TMEM45A (and/or of other genes from Table 1) in a non-cancer sample consisting of the original and/or native non-cancer cells.
  • these methods further comprise the step of comparing the expression level in the (cells of) the cancer sample and in the (cells of) the non cancer sample, preferably wherein this non cancer sample is obtained from the (same) patient suffering of cancer (for instance a normal breast tissue obtained from the same patient suffering from breast cancer) .
  • TMEM45A protein encoded by TMEM45A gene is quantified (possibly both truncated TMEM45A protein and/or alternatively spliced mRNA and full-length protein and/or mRNA is/are quantified).
  • the expression level of TMEM45A (and/or of other genes from Table 1), when considered as high, represents a worse prognosis and/or a need to select (or to further add) another treatment (including a treatment to inhibit TMEM45A over-expression) and/or a need to avoid (standard) chemotherapy (especially based on taxol or on etoposide) .
  • TMEM45A (and/or of other genes from Table 1) is depicted as a ratio of TMEM45A (and/or of other genes from Table 1) expression in the cancer sample, versus in the normal tissue.
  • a high expression level corresponds to an overexpression in the cancer (tumor) sample of at least 2-fold, preferably at least 3- fold or even 10-fold higher than in the non-cancer sample (but possibly not more than 500-fold or not more than 100- fold) .
  • a related aspect is a diagnostic kit comprising tools for measuring the expression of TMEM45A (and/or of other genes from Table 1) gene.
  • the preferred tools for measuring the expression of TMEM45A gene are for measuring TMEM45A mRNA content, such as primers and probes specifically recognizing parts of the corresponding TMEM45A cDNA (possibly tools for quantifying full-length cDNA and/or tools for quantifying a part (e.g. closer to 5' -end and/or closer to 3' -end) of this cDNA) .
  • TMEM45A gene Alternatively tools for measuring the expression of TMEM45A gene are specific antibodies directed against the protein encoded by this TMEM45A gene (or mRNA) , and/or parts thereof (such as antibodies specifically recognizing epitope (s) close (r) to N-terminal end, and/or epitope (s) close (r) to C-terminal end).
  • the kit of the present invention comprises tools for measuring expression of a (1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or even all the) gene from Table 1, more preferably SPAG4 (possibly in addition to at least another gene of this table) .
  • the kit of the present invention comprises tools for measuring the expression level of less than 100 (different) genes.
  • the kit of the present invention consists (essentially) of tools for measuring the expression level of TMEM45A gene (possibly in addition of tools for measuring the expression of a gene from Table 1 ) .
  • the term "consists essentially of” refers to the presence of tools for measuring the expression level of TMEM45A gene, and also of tools for measuring the expression level of up to a few other genes, such as control genes and/or one of several genes of Table 1.
  • the present invention also relates to the use of this kit for prognosticating the outcome of a cancer or for predicting the response to a chemotherapy treatment of a cancer and/or for monitoring the response to a chemotherapy treatment of a cancer.
  • Another related aspect of the present invention is chemotherapy (such as Paclitaxel or etoposide) for use (or for the manufacture of a medicament for the treatment of) in a patient suffering of a cancer, wherein TMEM45A expression (and/or of other genes from Table 1) in a cancer sample is less than 2-fold higher than in original and/or native non-cancer sample.
  • chemotherapy such as Paclitaxel or etoposide
  • TMEM45A expression and/or of other genes from Table 1
  • Another related aspect of the present invention is an anti TMEM45A (a drug and/or a compound that directly or indirectly inhibits TMEM45A overexpression and/or that reduces TMEM45A amount) for use in the treatment of a solid tumor cancer affecting a (human) patient (or for the manufacture of a medicament for the treatment of a solid tumor cancer), preferably in combination with a (another) chemotherapeutic drug such as hypoxia-inducing drugs and/or taxol and/or etoposide, and preferably in patients having high TMEM45A level (in their cancer cells) .
  • a chemotherapeutic drug such as hypoxia-inducing drugs and/or taxol and/or etoposide
  • MDA-MB-231 breast cancer cells were incubated with or without paclitaxel or epirubicin under normoxia or hypoxia, and caspase 3 activity and cell death, evidenced by LDH release, were assessed.
  • Paclitaxel and epirubicin did trigger apoptosis as well as cell death as shown by an about 2-fold increase in caspase 3 activity and LDH release in normoxia.
  • hypoxia inhibited the paclitaxel- induced increase in caspase 3 activity and LDH release (return to the baseline) .
  • DNA fragmentation and nuclear fragmentation were also assessed. For the latter, the cells were fixed and nuclei were labelled with fluorescent probe DAPI and observed with fluorescent microscopy. An increase in DNA fragmentation was observed in the presence of paclitaxel under normoxia, which was significantly decreased by hypoxia. Moreover, fragmented nuclei were observed in cells exposed to paclitaxel under normoxia but neither in cells exposed to paclitaxel under hypoxia nor in cells that were not incubated with paclitaxel.
  • Unsupervised hierarchical clustering was performed without any gene selection in order to group the conditions on the basis of their similarity measured over all probe sets on the array. Unsupervised cluster analysis using centered correlation and average linkage showed that control cells were well separated from drug-treated cells.
  • hypoxia was separated from normoxia while it was not the case for epirubicin- treated cells.
  • the inventors then compared differences and similarities in gene expression modifications in these conditions and genes were sorted to select only those with a high difference in expression between cells exposed to paclitaxel in normoxia ("N tax”) and cells exposed to paclitaxel in hypoxia (“H tax”), which could therefore be involved in the hypoxia-induced protection against paclitaxel-induced apoptosis.
  • the probe sets were ranked in ascending order of the p values of their differential expression between "N tax” and "H tax", and only highly significant ones with a p value lower than 0.005 were selected. A second round of selection of probe sets was then performed by keeping only those with a minimum fold change of at least 4 times between these 2 conditions.
  • Table 1 shows the 27 genes (from 31 probe sets) selected on the basis of their p value and fold change between "N tax” and "H tax”. [0073] Of note is transmembrane protein 45A
  • TMEM45A which expression was increased up to 16 times between these two conditions and was increased under hypoxic condition with or without paclitaxel but not in the presence of epirubicin.
  • TMEM45A is involved in the hypoxia-induced protection against paclitaxel-induced apoptosis
  • transcriptome data obtained for TMEM45A was then performed using single SYBR Green quantitative real time PCR assays for TMEM45A. Good correlation between relative transcript abundance data obtained by Affymetrix arrays and by real time RT-PCR was observed.
  • siRNA directed against TMEM45A A concentration of 50nM of siRNA was high enough to specifically inhibit the expression of TMEM45A while the RISC-Free negative control siRNA had no effect.
  • TMEM45A is also involved in the hypoxia- induced protection of HepG2 cells against etoposide-induced apoptosis .
  • the inventors further used another experimental model: HepG2 hepatocellular carcinoma cells exposed to etoposide.
  • the inventors wanted to determine if TMEM45A could also be involved in the protection of HepG2 cells against apoptosis induced by etoposide under hypoxia.
  • TMEM45A mRNA expression was shown to be increased by 5.5 fold in HepG2 cells incubated in the presence or in the absence of etoposide incubated under hypoxia. This increase correlated with the protective effect of hypoxia against etoposide-induced apoptosis. The inventors then determined that a concentration of 50 nM of TMEM45A siRNA was high enough to specifically inhibit TMEM45A mRNA expression while the RISC-Free control siRNA had no effect.
  • Caspase 3 activity was then assessed in cells transfected with TMEM45A or negative control siRNA before being incubated under normoxia or hypoxia in the presence or in the absence of etoposide. Caspase 3 activity was significantly increased for TMEM45A siRNA transfected HepG2 cells incubated with etoposide under hypoxia. No modification was observed in control cells and in cells incubated with etoposide under normoxia.
  • the caspase 3 activity measured for anti-TMEM45A siRNA transfected cells incubated under hypoxia with etoposide reached similar level than the activity measured for non transfected cells incubated in normoxia with etoposide, indicating that the protection was completely reversed when TMEM45A was silenced .
  • TMEM45A overexpression is associated with a high risk of breast cancer recurrence
  • the inventors then performed survival analysis using the Kaplan-Meier method on data from a study involving 286 patients with primary breast cancer and available clinical parameters. These patients were allocated to one of two subgroups of 143 patients stratified by TMEM45A expression. Kaplan-Meier graph compares the disease-free survival for groups of patients high and low TMEM45A expression (Fig. 2) . The results show that patients whose tumors had high TMEM45A expression had a significantly lower relapse-free survival than those whose tumors had a low TMEM45A expression (P ⁇ 0.01).
  • TMEM45A expression was 7-fold higher in these cancer patients.
  • TMEM45A expression was 2.5-fold higher in these cancer patients.
  • the type 1 tumors (which, due to its histological features, is associated to a worse prognosis) had a 3.5 fold induction of TMEM54A, while the type 2 tumors (associated to a better prognosis) had no induction of TMEM54A expression (same level as in healthy tissue) .
  • the inventors then treated patient suffering from several cancers with chemotherapeutic drugs such as taxol or etoposide and measured better relapse-free response in patients having (and keeping) low TMEM45A expression level in tumor sample.
  • chemotherapeutic drugs such as taxol or etoposide
  • TMEM45A overexpression in patients .

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Abstract

La présente invention concerne une méthode permettant de pronostiquer les conséquences d'un cancer, de prédire la réaction à un traitement chimiothérapique d'un cancer ou de surveiller la réaction à un traitement chimiothérapique d'un cancer, comportant les étapes qui consistent à mesurer le niveau d'expression du gène TMEM45A dans un échantillon.
EP13727840.4A 2012-07-12 2013-05-31 Méthode et trousse permettant de prédire ou de surveiller la réaction d'un patient cancéreux à la chimiothérapie, à partir de la mesure du niveau d'expression du gène tmem45a Withdrawn EP2872645A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13727840.4A EP2872645A1 (fr) 2012-07-12 2013-05-31 Méthode et trousse permettant de prédire ou de surveiller la réaction d'un patient cancéreux à la chimiothérapie, à partir de la mesure du niveau d'expression du gène tmem45a

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP12176145 2012-07-12
EP2013053588 2013-02-22
PCT/EP2013/061286 WO2014009055A1 (fr) 2012-07-12 2013-05-31 Méthode et trousse permettant de prédire ou de surveiller la réaction d'un patient cancéreux à la chimiothérapie, à partir de la mesure du niveau d'expression du gène tmem45a
EP13727840.4A EP2872645A1 (fr) 2012-07-12 2013-05-31 Méthode et trousse permettant de prédire ou de surveiller la réaction d'un patient cancéreux à la chimiothérapie, à partir de la mesure du niveau d'expression du gène tmem45a

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EP2872645A1 true EP2872645A1 (fr) 2015-05-20

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CN113293208B (zh) * 2020-02-21 2022-05-03 中国农业大学 与肺癌增殖和转移相关的分子标志物及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008077165A1 (fr) * 2006-12-22 2008-07-03 Austrian Research Centers Gmbh - Arc Ensemble de marqueurs tumoraux
US20090239223A1 (en) * 2006-07-13 2009-09-24 Siemens Healthcare Diagnostics Inc. Prediction of Breast Cancer Response to Taxane-Based Chemotherapy

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2791309A1 (fr) * 2010-02-05 2011-08-11 Myriad Genetics, Inc. Signatures du gene associe a l'hypoxie pour la classification du cancer
WO2012022634A1 (fr) * 2010-08-16 2012-02-23 Institut National De La Sante Et De La Recherche Medicale (Inserm) Classification, diagnostic et pronostic du myélome multiple

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090239223A1 (en) * 2006-07-13 2009-09-24 Siemens Healthcare Diagnostics Inc. Prediction of Breast Cancer Response to Taxane-Based Chemotherapy
WO2008077165A1 (fr) * 2006-12-22 2008-07-03 Austrian Research Centers Gmbh - Arc Ensemble de marqueurs tumoraux

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANNE P. G CRIJNS ET AL: "Survival-Related Profile, Pathways, and Transcription Factors in Ovarian Cancer", PLOS MEDICINE, vol. 6, no. 2, 3 February 2009 (2009-02-03), US, pages e1000024, XP055360913, ISSN: 1549-1277, DOI: 10.1371/journal.pmed.1000024 *
See also references of WO2014009055A1 *

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