Biomarker TFF1 for predicting effect of C-MET inhibitor
A method of predicting an effect of a c-Met inhibitor and/or selecting a subject for application of a c-Met inhibitor using TFF1, a method of monitoring an effect of a c-Met inhibitor using TFF1, and a method of treating and/or preventing cancer including administering a c-Met inhibitor to the selected subject.
1. A method of selecting a subject with gastric or lung cancer for treatment with a c-Met inhibitor, the method comprising
measuring in a biological sample from a subject with gastric or lung cancer the level of at least one selected from the group consisting of a TFF1 protein level and a TFF1 mRNA level,
and administering the c-Met inhibitor to the subject if the level of the TFF1 protein or mRNA in the biological sample is lower than that of a reference sample which is obtained from a patient for whom the c-Met inhibitor does not exhibit its effect, wherein the c-Met inhibitor is an anti-c-Met antibody.
2. The method of claim 1 , wherein the step of measuring comprises:
adding a material to the biological sample that interacts with the at least one selected from the group consisting of a TFF1 protein and a TFF1 mRNA to form a reaction mixture, wherein the material is a polynucleotide or antibody;
quantifying the level of at least one selected from the group consisting of a TFF1 protein and a TFF1 mRNA in the reaction mixture.
3. The method of claim 1 , further comprising measuring the level of at least one selected from the group consisting of c-Met protein and c-Met mRNA in the biological sample.
4. The method of claim 1 ,
wherein the anti-c-Met antibody is selected from the group consisting of (1) onartuzumab, LY2875358, rilotumumab, and an antibody comprising
a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 2, a CDR-H3 of SEQ ID NO: 3, a CDR-L1 of SEQ ID NO: 10, a CDR-L2 of SEQ ID NO: 11, and a CDR-L3 of SEQ ID NO: 13,
a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 2, a CDR-H3 of SEQ ID NO: 3, a CDR-L1 of SEQ ID NO: 106, a CDR-L2 of SEQ ID NO: 11, and a CDR-L3 of SEQ ID NO: 13,
a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 2, a CDR-H3 of SEQ ID NO: 3, a CDR-L1 of SEQ ID NO: 10, a CDR-L2 of SEQ ID NO: 11, and a CDR-L3 of SEQ ID NO: 12,
a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 2, a CDR-H3 of SEQ ID NO: 3, a CDR-L1 of SEQ ID NO: 10, a CDR-L2 of SEQ ID NO: 11, and a CDR-L3 of SEQ ID NO: 14,
a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 2, a CDR-H3 of SEQ ID NO: 3, a CDR-L1 of SEQ ID NO: 10, a CDR-L2 of SEQ ID NO: 11, and a CDR-L3 of SEQ ID NO: 15, or
a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 2, a CDR-H3 of SEQ ID NO: 3, a CDR-L1 of SEQ ID NO: 10, a CDR-L2 of SEQ ID NO: 11, and a CDR-L3 of SEQ ID NO: 16.
5. The method of claim 1 , wherein the measuring step further comprises determining:
i) a ratio of average mRNA expression level of TFF1 gene/average mRNA expression level of GAPDH gene is about 0.59 or less;
ii) a ratio of average mRNA expression level of TFF1 gene/average mRNA expression level of HPRT1 gene is about 1.24 or less; or
iii) a ratio of average mRNA expression level of TFF1 gene/average mRNA expression level of reference genes is about 0.72 or less, wherein the reference genes comprise EEF1A1, RPL23A, TPT1, HUWE1, MATR3, SRSF3, HNRNPC, SMARCA4, WDR90, and TUT1.
6. The method of claim 1 , wherein the subject has gastric cancer.
7. The method of claim 1 , wherein the subject has lung cancer.