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Application of NY-ESO-1 in diagnosis and treatment of microsatellite instability intestinal cancer

A NY-ESO-1, instability technology, applied in the fields of biology and medicine, can solve problems such as not recommending chemotherapy and microsatellite instability

Inactive Publication Date: 2017-01-25
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, the treatment of colorectal cancer is still limited to surgery, chemotherapy and radiotherapy. The main treatment method for metastatic colorectal cancer is still chemotherapy, but the 2011 edition of "NCCN Clinical Practice Guidelines for Colorectal Cancer" clearly pointed out that microsatellite Patients with stable (Microsatellite instability, MSI) colorectal cancer will not benefit from adjuvant chemotherapy with 5-fluorouracil (5-Fu). Therefore, it is recommended that all patients under the age of 50 should be considered for MSI testing. (High-frequency microsatellite instability, MSI-H) patients are not recommended to use chemotherapy

Method used

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  • Application of NY-ESO-1 in diagnosis and treatment of microsatellite instability intestinal cancer
  • Application of NY-ESO-1 in diagnosis and treatment of microsatellite instability intestinal cancer
  • Application of NY-ESO-1 in diagnosis and treatment of microsatellite instability intestinal cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0113] Example 1 Clinical retrospective analysis of the impact of NY-ESO-1 expression differences on the survival time of patients under different microsatellite status

[0114] In this example, 186 clinical samples were collected from 2005 to 2009, and their microsatellite status was determined through microsatellite typing analysis. Among them, 123 cases of MSS and 63 cases of MSI-H patients were analyzed by immunohistochemical method. The expression of NY-ESO-1 in tissues showed that the proportion of positive expression of NY-ESO-1 in MSI-H was 57.14%, which was significantly higher than that in MSS.

[0115] The influence of NY-ESO-1 expression differences in different microsatellite states on the survival time of patients was analyzed retrospectively. In the MSI-H group, the three-year survival rate of patients with positive NY-ESO-1 expression was 74.18%, while the three-year survival rate of patients with negative NY-ESO-1 expression was 55.71% figure 1 A); while in t...

Embodiment 2

[0116] Example 2 Verification of high expression of NY-ESO-1 in MSI colorectal cancer

[0117] Adherent tumor cells were digested with trypsin, collected by centrifugation and washed twice with PBS, 1×10 6 Cells, RNA extraction kit, extract total RNA from cells, and store at -80°C after final concentration and purity determination. Take 2 μg of total cellular RNA and synthesize cDNA by reverse transcription according to the instructions of the reverse transcription kit, react at 42°C for 30 minutes, inactivate at 99°C for 5 minutes, then add 16 μl of double distilled water to dilute, which can be used as a template for qPCR reaction. Use MAGE-A4, NY-ESO-1, NY-ESO-2 and Actin quantitative PCR primers (F: 5'-CAGACCACCGCCAACTGCA-3' (SEQ ID NO.: 3); R: 5'-TGAGGGAGGCTGAGCCAAA -3'(SEQ ID NO.:4)), using Green Realtime PCR Master Mix for quantitative PCR amplification. Such as figure 2 As shown in A.

[0118] Adherent tumors were digested with trypsin to make a single cell susp...

Embodiment 3

[0119] Example 3 Using NY-ESO-1 expression to classify intestinal cancer microsatellites

[0120] Double-blind determination was carried out by using the intestinal cancer specimens with known microsatellite typing in Example 1, so as to classify the intestinal cancer specimens according to the positive expression of NY-ESO-1. The results showed that the sensitivity of judging microsatellite instability colorectal cancer based on the expression of NY-ESO-1 was 90%, and the specificity was 78%. Therefore, colorectal cancer can be classified according to microsatellite stability according to the expression of NY-ESO-1.

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Abstract

The invention provides application of NY-ESO-1 in diagnosis and treatment of the microsatellite instability intestinal cancer. Specifically, the invention provides application of an NY-ESO-1 gene, a protein or a detection reagent in preparation of a kit for (a) diagnosing the microsatellite instability intestinal cancer, and / or (b) judging prognosis of an intestinal cancer patient. Furthermore, an experiment shows that by the use of DC cells stimulated by NY-ESO-1, generation of T cells can be effectively stimulated, and the T cells have the effect of inhibiting the tumor of the microsatellite instability intestinal cancer. By the use of the gene and the protein, a treatment scheme for the intestinal cancer patient and forecasting of prognosis can be guided.

Description

technical field [0001] The present invention relates to the fields of biology and medicine, and more specifically relates to the application of NY-ESO-1 in microsatellite unstable colorectal cancer immunotherapy. Background technique [0002] Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Its incidence ranks third and second among malignant solid tumors in men and women, respectively, and ranks fourth in cancer-related deaths. In recent years, the incidence of colorectal cancer has been increasing, and the increase rate in my country is twice the international average growth rate (2%), especially in Shanghai and other southeast coastal developed cities, where the incidence rate has reached the second place in solid tumors (30%. / 100,000), seriously threatening human health and quality of life. [0003] At present, the treatment of colorectal cancer is still limited to surgery, chemotherapy and radiotherapy. The main treatment method for meta...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68G01N33/574A61K39/00A61K48/00A61K39/395A61K31/7068A61K38/17A61K45/06A61P35/00
CPCA61K38/17A61K45/06C12Q1/6886G01N33/57419C12Q2600/118C12Q2600/136C12Q2600/158A61K39/4611A61K2239/52A61K39/4615A61K39/4622A61K39/464488A61K39/395A61K48/00A61K31/7068C12Q1/68G01N33/574
Inventor 万涛虞淦军曹雪涛
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY