Method of predicting effect of medicinal therapy on cancer
The present invention provides a factor capable of predicting an effect of a medicinal therapy on a cancer such as HER2 positive cancer. More specifically, the present invention provides a method of predicting the effect of the medicinal therapy on the cancer, comprising: (1) analyzing a methylation level of a cytosine residue in one or more CpG sites present within a nucleotide sequence in a promotor region, an untranslated region or a translated region of HSD17B4 gene in a sample taken from a human subject; and (2) predicting the effect of the medicinal therapy on the cancer based on the analyzed methylation level.
1. A method of treating a HER2-positive breast cancer in a human subject, comprising:
measuring the methylation level of a cytosine residue in one or more CpG sites present within a nucleotide sequence in an untranslated region of HSD 17B4 gene, wherein the untranslated region consists of SEQ ID NO:1, in a breast cancer cell-containing sample taken from a human subject suffering from the HER2-positive breast cancer;
predicting an effect of a treatment with a trastuzumab on the HER2-positive breast cancer based on the measured methylation level, wherein increased methylation level of the cytosine residue in the one or more CpG sites indicates that the trastuzumab is effective for the treatment;
selecting a human subject with high methylation level of the cytosine residue in the one or more CpG sites; and
treating the selected human subject with the trastuzumab.
2. A method of selecting a treatment with a trastuzumab on a HER2-positive breast cancer, comprising:
measuring a methylation level of a cytosine residue in one or more CpG sites present within a nucleotide sequence in an untranslated region of HSD 17B4 gene, wherein the untranslated region consists of SEQ ID NO:1, in a breast cancer cell-containing sample taken from a human subject suffering from the HER2-positive breast cancer; and
selecting the trastuzumab as the treatment for the HER2-positive breast cancer based on the measured methylation level, wherein increased methylation level of the cytosine residue in the one or more CpG sites compared to a control population in which said treatment is ineffective, indicates that the trastuzumab is effective for the treatment, and treating the human subject with the trastuzumab, wherein the measuring comprises measuring with at least one means selected from the group consisting of bisulfite, primers, a nucleic acid probe, a restriction enzyme, an anti-methylated cytosine antibody, and a nanopore.
3. The method of claim 1 , comprising:
measuring a methylation level of a cytosine residue in one or more CpG sites present within a nucleotide sequence in an untranslated region of HSD 17B4 gene, wherein the untranslated region consists of SEQ ID NO:1, in a breast cancer cell-containing sample taken from a human subject suffering from the HER2-positive breast cancer;
predicting an effect of a treatment with a trastuzumab in combination with another anticancer agent on the HER2-positive breast cancer based on the measured methylation level, wherein increased methylation level of the cytosine residue in the one or more CpG sites indicates that the trastuzumab in combination with another anticancer agent is effective for the treatment;
selecting a human subject with high methylation level of the cytosine residue in the one or more CpG sites; and
treating the selected human subject with the trastuzumab in combination with another anticancer agent.
4. The method of claim 1 , wherein the sample is at least one sample selected from the group consisting of a blood, a body fluid, a breast cancer tissue, and a breast cancer cell.
5. The method of claim 1 , wherein the CpG site is a CpG site normally present between positions 56 and 94 from the transcription start site at position 11 of SEQ ID NO: 1.
6. The method of claim 1 , wherein the CpG site is a CpG site normally present at positions 92 and 93 from the transcription start site at position 11 of SEQ ID NO: 1.
7. The method of claim 1 , further comprising measuring the expression of estrogen receptor in the breast cancer cell-containing sample.
8. The method of claim 1 , wherein the measuring comprises measuring with at least one means selected from the group consisting of bisulfite, primers, a nucleic acid probe, a restriction enzyme, an anti-methylated cytosine antibody, and a nanopore.
9. The method of claim 1 , wherein the measuring is performed by a bisulfite sequencing method, a bisulfite pyrosequencing method, a methylation specific PCR method, a restriction enzyme landmark genome scanning (RLGS) method, a single nucleotide primer extension (SNuPE) method, a CpG island microarray method, a MethyLight method, a COBRA method, a mass spectroscopy (mass array) method, use of a methylation specific restriction enzyme, a high resolution melting analysis (HRM) method, a nanopore analysis method, an ICON probe method, a methylation specific MLPA method, or an immunoassay.