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Marker for predicting efficacy of neoadjuvant chemotherapy for breast cancer patients and application of marker

A breast cancer, patient technology, applied in the determination/examination of microorganisms, biochemical equipment and methods, DNA/RNA fragments, etc., can solve problems such as incomplete elucidation of molecular mechanisms, influence on treatment plans, and differences in efficacy.

Active Publication Date: 2020-03-27
CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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Problems solved by technology

However, as mentioned above, resistance to chemotherapy drugs is a key challenge in the treatment of breast cancer, especially for Luminal breast cancer, which accounts for the majority of breast cancer.
The response of breast cancer cells to epirubicin is closely related to the effectiveness of treatment, which in turn affects the choice of treatment options and affects the prognosis of patients
The regulatory process of chemotherapeutic drug sensitivity involves many factors, specific genetic or epigenetic alterations and cancer-associated genomic plasticity underlie drug resistance, however, the underlying molecular mechanisms have not been fully elucidated
[0005] Previous studies have shown that related genetic susceptibility genes involved in the metabolism or action of chemotherapy drugs, if germline variation occurs, may cause differences in the efficacy of patients by affecting the ability of apoptosis

Method used

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  • Marker for predicting efficacy of neoadjuvant chemotherapy for breast cancer patients and application of marker
  • Marker for predicting efficacy of neoadjuvant chemotherapy for breast cancer patients and application of marker
  • Marker for predicting efficacy of neoadjuvant chemotherapy for breast cancer patients and application of marker

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Experimental program
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Effect test

Embodiment 1

[0031] The screening of embodiment 1 candidate SNP

[0032] 1. Preliminary screening of candidate SNPs

[0033]Firstly, genes related to resistance / sensitivity to epirubicin (NCI No. 256942) or docetaxel (NCI No. 628503) were screened in the CellMiner database (http: / / discover.nci.nih.gov / cellminer / ). Using Pearson's correlation coefficient and growth inhibition value (GI50, a measure of cell line sensitivity) for gene expression below -0.4 or above 0.4 as a criterion, 284 epirubicin genes and 228 docetaxel genes were obtained. Considering redundancy, 511 genes were removed and considered as potential biomarkers of resistance or susceptibility. We then obtained all SNPs located 5 kb upstream and genes in Han with a minor allele frequency (MAF) >0.05 from the 1000 Genomes Project (http: / / www.1000genomes.org / ). Finally, the ANNOVAR software tool was applied to annotate the function of the genetic variation, and 14 SNPs were prioritized as candidate regulatory SNPs for the foll...

Embodiment 2

[0064] Embodiment 2, biological verification

[0065] 1. Luciferase reporter assay

[0066] Plasmid construction

[0067] DNA fragments containing rs6484711[G] or rs6484711[A] were subcloned into pGL3-Basic vector (Promega, USA), respectively. The full-length cDNA of ABTB2 was subcloned into pcDNA3.1(+) vector (Invitrogen, USA). All recombinant plasmids were synthesized and sequence verified by Genewiz (Suzhou, China).

[0068] cell culture

[0069]Human MCF-7 and T-47D BC cell lines were purchased from China Type Culture Collection (Wuhan, China). Cell lines were cultured in Dulbecco's Modified Eagle's Medium (DMEM) or Roswell Park Memorial Institute (RPMI) 1640 medium (Gibco, USA), supplemented with 10% fetal bovine serum (FBS; Gibco, USA) and 1% antibiotics (100 U / mL penicillin and 0.1 mg / mL streptomycin) at 37°C in a humidified environment of 5% CO2. All cell lines were routinely tested by DNA sequencing using the Applied Biosystems AmpF / STR Identifier kit and teste...

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Abstract

The invention provides rs6484711 as a marker for predicting the efficacy of neoadjuvant chemotherapy for breast cancer. Results prove that the rs6484711 variant participates in tumor cell resistance to the neoadjuvant chemotherapy containing epirubicin and docetaxel by regulating the expression of ABTB2, so that the marker is helpful for personalized treatment of the neoadjuvant chemotherapy and is expected to be a target for development of novel therapeutic drugs.

Description

technical field [0001] The present invention belongs to the field of cancer, in particular, relates to a marker for predicting the curative effect of neoadjuvant chemotherapy in patients with breast cancer and its application, especially to neoadjuvant chemotherapy containing epirubicin and docetaxel for luminal breast cancer. The efficacy of chemotherapy. Background technique [0002] Breast cancer (BC) is the most common malignancy in women, accounting for approximately 25.2% of cancer cases and 14.7% of cancer-related deaths worldwide. Early breast cancer is considered curable. Neoadjuvant chemotherapy (NAC) can increase the breast-conserving rate of breast cancer, and can also give some inoperable patients the chance of surgery. It has become the standard therapy for patients with locally advanced breast cancer. Pathological complete response (pCR) is proposed as the most common clinical observation endpoint in neoadjuvant therapy and is associated with long-term survi...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/106C12Q2600/156C12Q2600/158C12Q2600/172
Inventor 袁芃胡南林
Owner CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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