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Triple-negative breast cancer marker and applications of triple-negative breast cancer marker in diagnosis and therapy

A technology for triple-negative breast cancer and breast cancer, which is applied in the field of oncology and diagnosis, and can solve problems such as the lack of targeted treatment methods and the inability to develop drugs

Active Publication Date: 2016-02-24
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For triple-negative breast cancer, due to the lack of specific cell surface molecular markers, targeted drug development cannot be carried out
At present, the first-line treatment drugs for triple-negative breast cancer are broad-based cytotoxic chemotherapy drugs, and there is still a lack of effective targeted therapies

Method used

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  • Triple-negative breast cancer marker and applications of triple-negative breast cancer marker in diagnosis and therapy
  • Triple-negative breast cancer marker and applications of triple-negative breast cancer marker in diagnosis and therapy
  • Triple-negative breast cancer marker and applications of triple-negative breast cancer marker in diagnosis and therapy

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0193] Procr is highly expressed in triple negative breast cancer samples and cell lines

[0194] 1.1 Immunohistochemical staining

[0195] Using the method of immunohistochemical staining, the expression of Procr was detected in the four human breast cancer subtypes.

[0196] Specific steps: Collect tissue sections of 311 clinical samples of human breast cancer.

[0197] The results of immunohistochemical staining are as follows figure 1 As shown, in triple-negative breast cancer samples, about 86% were Procr positive (n=113); while in LummalA, LuminalB, Her2 positive breast cancer, the Procr positive rate was significantly lower, respectively (about 14%, n= 79), (about 12%, n=58) and (26%, n=61).

[0198] This result shows that Procr is widely and highly expressed in triple-negative breast cancer and can be used as a molecular marker for the diagnosis of triple-negative breast cancer.

[0199] 1.2 Quantitative PCR

[0200] Real-timeQPCR method was used to detect different subtypes of ...

Embodiment 2

[0203] Procr-positive breast cancer tumor cells are more tumorigenic

[0204] Specific steps: After the MMTV-Wnt1 mice that had formed breast tumors were sacrificed, their tumor tissues were taken out and cut into pieces, and the tissue pieces were digested with collagenase. The digested mammary glands are treated with red blood cell lysate and then trypsinized to obtain single cells. With the help of a flow cytometer, use anti-Ter119-FITC, anti-CD31-FITC, anti-CD45-FITC antibodies to remove blood system-related components in the breast, and use anti-CD29-APC and anti-CD24-PE- Cy7 distinguishes breast tumor epithelial cells, and then uses anti-Procr-PE to obtain Procr positive and Procr negative breast tumor epithelial cells.

[0205] The sorted Procr negative and positive cells were injected into the fourth pair of mammary glands on the right side of female nude mice at 3 weeks. Observe the formation of the tumor after 3 months.

[0206] The result is image 3 Shown. Procr-posit...

Embodiment 3

[0210] Procr-positive normal mouse mammary stem cells show typical epithelial-mesenchymal transformation properties

[0211] Specific steps: After euthanizing the adult female mouse, take out the breast tissue and cut it into pieces, and digest the tissue block with collagenase. The digested mammary glands are treated with red blood cell lysate and then trypsinized to obtain single cells. With the help of a flow cytometer, use anti-Ter119-FITC, anti-CD31-FITC, anti-CD45-FITC antibodies to remove blood system-related components in the breast, and use anti-CD29-APC and anti-CD24-PE- Cy7 distinguishes the basal cells of the breast epithelium, and then uses anti-Procr-PE to obtain Procr-positive and Procr-negative breast epithelial cells.

[0212] The obtained Procr-positive and Procr-negative cells were subjected to RNA sequencing. Through cluster analysis, it was found that the Procr-positive breast stem cells had obvious epithelial-mesenchymal transition characteristics.

[0213] Su...

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Abstract

The present invention relates to a triple-negative breast cancer marker and applications of the triple-negative breast cancer marker in diagnosis and therapy, and particularly provides uses of a protein C receptor (Procr protein) in preparation of diagnosis reagents or kits for triple-negative breast cancer detection. The research results show that the Procr is the characteristic triple-negative breast cancer marker, such that the Procr can be adopted as the triple-negative breast cancer diagnosis marker. The present invention further provides a method and a pharmaceutical composition for triple-negative breast cancer therapy based on Procr.

Description

Technical field [0001] The invention relates to the field of oncology and diagnosis. More specifically, the present invention relates to a marker for diagnosing triple-negative breast cancer and its application in diagnosis and treatment. Background technique [0002] Human breast cancer is roughly divided into four subtypes clinically. Three subtypes (LuminalA, LuminalB, Her2 positive) of breast cancer are known to be formed by breast luminal cell lesions, and their specific cell surface molecular markers are known as estrogen receptor (Estrogen Receptor) and progesterone receptor. (ProgesteroneReceptor) and EGF receptor (EGFReceptor, Her2). For these three types of breast cancer, there are now clinically targeted therapeutic target drugs (see Figure 14 ). [0003] Breast cancer that does not express the above three receptors is clinically diagnosed as triple-negative breast cancer. For triple-negative breast cancer, because there is no specific cell surface molecular marker, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68G01N33/68G01N33/574A61K45/00A61K48/00A61K39/395A61P35/00
Inventor 曾艺王代松
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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