Biomarker for measurement of response and prognosis of triple-negative breast cancer to anticancer agent

Patent metadata

Field	Value
Publication number	US-2020087733-A1
Application number	US-201816494557-A
Country	US
Kind code	A1
Filing date	Mar 8, 2018
Priority date	Mar 16, 2017
Publication date	Mar 19, 2020
Grant date	—

Abstract

The present disclosure discloses a biomarker capable of predicting the therapeutic response to anticancer agents and prognosis of triple-negative breast cancer patients, and the use thereof. A biomarker according to the present disclosure allows the provision of optimized personal therapeutic methods through correct personalized treatment, contributing to the quality and prolongation of life of patients.

First claim

1 . A biomarker for predicting response to anticancer agents and prognosis in triple-negative breast cancer, comprising: one or more biomarkers of a first group and one or more biomarkers of a second group,
wherein the one or more biomarkers of the first group consist of CCAAT/enhancer-binding protein delta (CEBPD), matrix metalloproteinase-20 (MMP20), and wntless Wnt ligand secretion mediator (WLS), the one or more biomarkers of the second group consist of anti-silencing function 1A histone chaperone (ASF1A), ALVEOLAR SOFT PART SARCOMA CHROMOSOME REGION (ASPSCR1), chromatin assembly factor 1 subunit B (CHAF1B), DNA methyltransferase 1 (DNMT1), GINS complex subunit 2 (GINS2), golgin subfamily A member 2B (GOLGA2P5), and spindle and kinetochore-associated protein 1 (SKA1), and the one or more biomarkers of the first group are up score genes showing resistance to the anticancer agent and increased expression in a patient with poor prognosis, and the one or more biomarkers of the second group are down score genes showing resistance to the anticancer agent and reduced expression in a patient with poor prognosis.

2 . The biomarker of claim 1 ,
wherein the biomarker comprises a nucleic acid or a protein.

3 . The biomarker of claim 1 ,
wherein the anticancer agents include taxane-based anticancer agents comprising docetaxel, paclitaxel, or cabazitaxel, vinca alkaloid anticancer agents comprising vincristine or vinblastine, anthracycline, 5-fluorouracil, or cyclophosphamide.

4 . The biomarker of any one of claim 1 ,
wherein the one or more biomarkers of the first group comprise CEBPD, and the one or more biomarkers of the second group comprise ASPSCR1, CHAF1B, and SKA1.

5 . A method of determining chemoresponse or prognosis in a patient with triple-negative breast cancer, the method comprising:
providing a biological sample derived from a target subject in need of the determination for the chemoresponse or prognosis; measuring an expression level of one or more biomarkers of the first group and one or more biomarkers of the second group, at a nucleic acid level or a protein level from the biological sample, wherein the one or more biomarkers of the first group consist of CCAAT/enhancer-binding protein delta (CEBPD), matrix metalloproteinase-20 (MMP20), and wntless Wnt ligand secretion mediator (WLS), and the one or more biomarkers of the second group consist of anti-silencing function 1A histone chaperone (ASF1A), ALVEOLAR SOFT PART SARCOMA CHROMOSOME REGION (ASPSCR1), chromatin assembly factor 1 subunit B (CHAF1B), DNA methyltransferase 1 (DNMT1), GINS complex subunit 2 (GINS2), golgin subfamily A member 2B (GOLGA2P5), and spindle and kinetochore-associated protein 1 (SKA1); and associating the target subject with chemoresistance and prognosis by comparing the results of the measuring with those of a reference group, wherein the one or more biomarkers of the first group are up score genes showing resistance to the anticancer agents with increased expression in a patient with poor prognosis, and the one or more biomarkers of the second group are down score genes showing resistance to the anticancer agents with reduced expression in a patient with poor prognosis.

6 . The method of claim 5 ,
wherein, in the associating, the reference group refers to a group of patients with triple-negative breast cancer, and provides an expression level determined for each biomarker in a sample derived from a patient having information on response to the anticancer agents and/or prognosis, and when, compared to the median or mean value of the reference group, an expression level of the one or more biomarkers of the first group increases and an expression level of the one or more biomarkers of the second group decreases, the target subject is determined to have poor prognosis, and when, compared to the median or mean value of the reference group, an expression level of the one or more biomarkers of the first group decreases and an expression level of the one or more biomarkers of the second group increases, the target subject is determined to have good prognosis.

7 . The method of claim 5 ,
wherein the measuring further comprises the steps of: determining a relative expression level of each of the one or more biomarkers of the first group and the one or more biomarkers of the second group, based on the measured expression level; calculating an up score by averaging the relative expression level of the one or more biomarkers of the first group; and calculating a down score by averaging the relative expression level of the one or more biomarkers of the second group, in the associating, the results of the reference group are shown in a scatter plot with x- and y-axes for the up score of the one or more biomarkers of the first group and the down score of the one or more biomarkers of the second group, respectively, wherein the up score and the down score are determined from the patients with triple-negative breast cancer and having information on response to the anticancer agents, and the scatter plot includes a first diagonal line passing through a point with x- and y-values for the median value of the up score and the median value of the down score, respectively, and having a slope determined by a denominator and a numerator, wherein the denominator is obtained by subtracting a minimum value of the up score from a maximum value of the up score, and the numerator is obtained by subtracting a minimum value of the down score from a maximum value of the down score, and in the associating, when the up score and the down score determined from the target subject are plotted in the scatter plot, and the point belongs to a region above the first diagonal line, the target subject is determined to have good response to the anticancer agents and good prognosis, and when the point belongs to a region below the first diagonal line, the target subject is determined to have poor response to the anticancer agents and poor prognosis.

8 . The method of any one of claim 5 ,
wherein the one or more biomarkers of the first group comprise CEBPD, and the one or more biomarkers of the second group comprise ASPSCR1, CHAF1B, and SKA1.

9 . The method of any one of claim 5 ,
wherein the anticancer agent comprises a taxane-based anticancer agent including docetaxel, paclitaxel, or cabazitaxel, a vinca alkaloid anticancer agent including vincristine or vinblastine, anthracycline, 5-fluorouracil, or cyclophosphamide.

10 . The method of any one of claim 5 , wherein the biological sample comprises breast tissue, whole blood, lymph, serum, urine, plasma, circulating cancer cell, or nipple aspirate.

Assignees

• Seoul Nat Univ R&Db Foundation
• Industry Academic Cooperation Foundation Of Sunchon National Univ
• Seoul Nat Univ Hospital

Inventors

• Han Wonshik
• Noh Dong-Young
• Lee Han-Byoel
• Kim Eun-Kyu
• Park Ae-Kyung
• Moon Hyeong-Gon

Classifications

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• G01N33/575

  for cancer · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title