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Immune molecule classification system for prostate cancer patients and application thereof

A technology of prostate cancer and immune molecules, applied in the field of biomedicine

Pending Publication Date: 2021-03-19
THE FIRST AFFILIATED HOSPITAL OF ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these immune checkpoint blockade (ICB) treatments are only effective for some patients, and the molecular characteristics of TME are closely related to the response to radiotherapy and chemotherapy and to ICB.

Method used

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  • Immune molecule classification system for prostate cancer patients and application thereof
  • Immune molecule classification system for prostate cancer patients and application thereof
  • Immune molecule classification system for prostate cancer patients and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Determination of immune subclasses:

[0026] 1. Patient collection:

[0027] ①A total of 1557 prostate cancer patients were included in the current study, whose information included available gene expression profiles, clinicopathological features, and recurrence-free survival records, and the research protocol flow was as follows: figure 1 shown;

[0028]② 495 patients from the Prostate Cancer Genome Atlas (TCGA-PRAD) were used as the training cohort, and three public cohorts from Memorial Sloan-Kettering Cancer Center (MSKCC), GSE70770, GSE116918 and GSE79021 were used as the validation cohort , a total of 993 prostate cancer patients were included in the study;

[0029] ③ The recurrence-free survival records of 69 formalin-fixed paraffin-embedded (FFPE) patients in the Urology Department of the First Affiliated Hospital of Anhui Medical University (AHMU-PC cohort) were collected;

[0030] ④ Based on the Illumina NovaSeq platform, the paired-end 150bp sequencing str...

Embodiment 2

[0051] Subtyping of immune subtypes established:

[0052] 1. Since the activated stromal response is negatively correlated with immune activation, 63.0% (126 / 200) of the patients with the immune subtype were characterized by high stromal enrichment scores (SESs) (such as image 3 A below picture);

[0053] 2. Transforming growth factor-β is considered a central mediator of immunosuppression in the immune microenvironment, while high levels of extracellular matrix cytokines (C-ECM) induced by activation of cancer-associated fibroblasts can recruit immune Inhibitory cells; as expected, Wnt / TGF-β, TGF-β1, and C-ECM signaling were found to be more active in the stromal-activated subtype, also known as the immunosuppressive subtype, than in the non-immune subtype (all P image 3 More enriched in A), the remaining 37.0% of patients (74 / 200) belonged to the immune activation subtype;

[0054] 3. Increased expression of IL-11, TGFB1, and TGFB2 in the immunosuppressive subtype compared...

Embodiment 3

[0060] Validation of the relationship between immune activation and good relapse-free survival and anti-PD-1 immunotherapy:

[0061] 1. Clinicopathological features are important indicators for evaluating the malignancy of prostate cancer. In the TCGA-PRAD cohort of patients under 60 years of age, relapse-free survival was better for the immune-activating subtype, lower for the immunosuppressive subtype, and intermediate for the non-immune subtype (P=0.033 ,like image 3 B);

[0062] 2. To test the potential ability of the immune molecular classification system in selecting candidates for anti-PD-1 / PD-L1 immunotherapy; the results showed that patients with immune activation subtypes responded better to anti-PD-1 immunotherapy (Bonferroni corrected P = 0.0079, as image 3 C).

[0063] In summary, combined with image 3 B-C, Patients in the immune activation category showed the best relapse-free survival outcomes and benefited more from anti-PD-1 / PD-L1 immunotherapy.

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Abstract

The invention provides an immune molecule classification system for prostate cancer patients and application of the immune molecule classification system, and relates to the technical field of biomedicine. According to the immune molecule classification system for the prostate cancer patient, the prostate cancer patient is divided into three subtypes, namely a non-immune subtype, an immune activation subtype and an immunosuppression subtype, and clinical anti-PD-1 / PD-L1 treatment is determined through classification. The defects in the prior art are overcome, a new classification system basedon immune characteristics is established, three immune phenotypes are established, it is prompted that immune response is a driving factor of prostate cancer prognosis, and a new thought is provided for immunotherapy of prostate cancer patients.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an immune molecule classification system for prostate cancer patients and its application. Background technique [0002] Prostate cancer is a malignant tumor with the second highest incidence rate and the fifth highest mortality rate among men. It not only brings great pressure to the world health system, but also poses a serious threat to men's health. Men with low-intermediate risk prostate cancer can be treated with minimally invasive ablation, radiation therapy, or radical prostatectomy. [0003] However, about 26%-30% of prostate cancer patients will enter the advanced stage within 5 years after diagnosis. Although androgen deprivation therapy (Androgen Deprivation Therapy, ADT) can be used for these advanced patients, they still face the outcome of rapidly entering the castration-resistant stage (CRPC), which will lead to their death in 2 to 4 years. For CRPC patients...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G16H50/20
CPCG16H50/20
Inventor 孟佳林张蒙陆晓凡周宇杰董柏君卞子辰胡先宇单凯军张坤宇张力郝宗耀梁朝朝
Owner THE FIRST AFFILIATED HOSPITAL OF ANHUI MEDICAL UNIV
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