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Prostatic cancer marker SPOP and application thereof in guiding of tumor treatment

A technology of prostate cancer and markers, applied in the direction of antineoplastic drugs, medical preparations containing active ingredients, drug combinations, etc., can solve the problems of poor prognosis, non-standard endocrine therapy, unreasonable prostate cancer, etc.

Inactive Publication Date: 2017-10-27
SHANGHAI CHANGHAI HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Androgen deprivation therapy is the main treatment for advanced prostate cancer. However, many scholars have found in clinical practice that although continuous androgen deprivation therapy is effective for nearly 90% of patients in the first treatment, almost all patients have It is inevitable to progress to androgen-independent prostate cancer within 2 to 3 years, and the prognosis of patients with the above outcomes is poor, and the median survival time is only 18 months
Different advanced prostate cancer patients have different responses to endocrine therapy. This phenomenon is called different sensitivity of prostate cancer to endocrine therapy in clinical practice. Based on international and domestic research, there is no effective method to accurately predict this difference in sensitivity. As a result, many patients with advanced prostate cancer have no choice but to accept unreasonable and irregular endocrine therapy

Method used

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  • Prostatic cancer marker SPOP and application thereof in guiding of tumor treatment
  • Prostatic cancer marker SPOP and application thereof in guiding of tumor treatment
  • Prostatic cancer marker SPOP and application thereof in guiding of tumor treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 SPOP binds and recognizes the SBC motif degrader of BRD2 / 3 / 4 protein to promote its ubiquitination and degradation

[0042] (1.1) Yeast two-hybrid system screening to identify the degradation target protein of SPOP

[0043] The present invention screens the target protein of SPOP through the yeast two-hybrid system, finds 246 positive clone strains including known DEK and SRC-3, and screens the target protein among them, among which the BET protein family has the highest number of hits, 52 clones were BRD2, 2 clones were BRD3, and 6 clones were BRD4 (eg figure 1 shown).

[0044] Co-immunoprecipitation (Co-IP) was performed in LNCaP cells, and Western Blot was performed using IgG or BRD2 / 3 / 4 antibodies to find that SPOP protein could bind to BRD2 / 3 / 4 protein ( figure 2 ). Therefore, SPOP protein can bind to BET protein family members.

[0045] (1.2) SPOP promotes BRD2 / 3 / 4 protein degradation

[0046] As mentioned above, SPOP protein can bind to BET protei...

Embodiment 2

[0052] The impact of embodiment 2 SPOP on the anti-tumor effect of BET protein inhibitor

[0053] (2.1) The expression level of BET protein in tumor tissues of patients with prostate cancer is up-regulated

[0054]The present invention finds that 13 prostate cancer samples contain SPOP mutations after performing whole genome sequencing, RNA sequencing, and Sanger sequencing on two sets of samples containing a total of 99 cases of primary prostate cancer. Immunohistochemical (IHC) analysis experiments showed that BRD2 / 3 / 4 protein staining was strongly positive in the vast majority of SPOP-mutated prostate tissues (BRD2: 85% (11 / 13), BRD3: 92% (12 / 13), BRD4 : 85% (11 / 13)) ( Figure 11 ). In contrast, in wild-type SPOP prostate cancer tissue samples, only a part of BRD2 / 3 / 4 protein staining was strongly positive (BRD2: 29% (25 / 86), BRD3: 34% (29 / 86), BRD4: 41% (35 / 86)), most BRD2 / 3 / 4 staining was weakly positive or negative (BRD2: 71% (61 / 86), BRD3: 66% (57 / 86), BRD4: 59% (51 / ...

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Abstract

The invention discloses a prostatic cancer marker SPOP. The SPOP marker comprises DNA of SPOP, mRNA or protein coded thereby, wherein the Pubmed Gene ID of the DNA sequence of the SPOP is 8405; the nucleotide sequence of the mRNA of the SPOP is shown as SEQ ID No.1; the protein sequence of the SPOP is shown as SEQ ID NO.2. The invention also discloses application of the SPOP marker in molecular subtyping of prostatic cancer and guiding of a BET inhibitor in treatment of prostatic cancer.

Description

technical field [0001] The invention belongs to the field of cancer guidance therapy, and specifically relates to the application of SPOP as a marker for molecular typing of prostate cancer and for guiding prostate cancer patients to use BET inhibitors for treatment. Background technique [0002] Prostate cancer (PCa) is a malignant tumor that seriously threatens men's health, accounting for the second place in cancer incidence and the sixth place in death rate in the world. The incidence of PCa in my country has been on a significant upward trend in recent years. Differences in sensitivity to hormone therapy in advanced prostate cancer. Androgen deprivation therapy is the main treatment for advanced prostate cancer. However, many scholars have found in clinical practice that although continuous androgen deprivation therapy is effective for nearly 90% of patients in the first treatment, almost all patients have It is inevitable to progress to androgen-independent prostate ...

Claims

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Application Information

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IPC IPC(8): C12Q1/68G01N33/574A61K45/00A61P35/00
CPCA61K45/00C12Q1/6886C12Q2600/112C12Q2600/136C12Q2600/156C12Q2600/158G01N33/57434G01N33/57484
Inventor 孙颖浩任善成黄浩杰
Owner SHANGHAI CHANGHAI HOSPITAL
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