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Sarcoma radiotherapy resistance-related diagnostic marker and application

A sarcoma and biomarker technology, applied in the field of molecular biology, can solve problems such as unconfirmed biological effects, achieve the effect of enhancing radiotherapy sensitivity and improving the huge difference

Active Publication Date: 2021-01-01
中国医科大学
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the biological role of KIF18B in sarcoma has not been confirmed

Method used

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  • Sarcoma radiotherapy resistance-related diagnostic marker and application
  • Sarcoma radiotherapy resistance-related diagnostic marker and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1 Survival analysis of key genes.

[0019] In the sarcoma radiotherapy patient group and sarcoma non-radiotherapy patient group, the expression of key genes was divided into high expression group and low expression group according to the median; Survival (R package) was used in Kaplan-Meier survival analysis; finally Survival curves were drawn using the Log-rank method.

[0020] The experimental results show as figure 1 As shown, in patients who did not receive radiotherapy, different expression levels of KIF18B did not have much effect on survival, while in patients with sarcoma treated with radiotherapy, patients with high expression of KIF18B and patients with lower expression had significantly worse survival. Prognosis, indicating that the high expression of KIF18B inhibits the sensitivity of sarcoma radiotherapy treatment.

Embodiment 2

[0021] Example 2 Cloning experiment.

[0022] Cell survival was assayed by performing clonogenic assays to determine whether inhibition of KIF18B expression enhanced the cytotoxic effects of radiotherapy. Three different sarcoma cell lines (HT1080, RD, MNNG / HOS) were used in the present invention.

[0023] First, different transfection-treated sarcoma cells were inoculated in six-well plates, including sh-NC negative control group, sh-KIF18B3 silencing group, and sh-KIF18B4 silencing group.

[0024] Radiation after 48 hours: use a SIEMENS linear accelerator for X-ray irradiation, the radiation doses are 0Gy, 2Gy, 4Gy, 6Gy and 8Gy, and the power is 2Gy / min.

[0025] After the cells were further cultured for 14 days, they were fixed with 70% ethanol and stained with Giemsa reagent, and cell colonies with more than 50 cells were counted.

[0026] The cell survival fraction was calculated, and the cell survival fraction (Surviving Fraction, SF)=the number of clones per well of t...

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Abstract

The invention belongs to the field of molecular biology, and particularly relates to a sarcoma radiotherapy resistance-related diagnostic marker and application. According to application of IF18B as asarcoma biomarker, the IF18B is highly expressed in sarcoma tissue, and tumor cell radiotherapy sensitivity can be improved by inhibiting kinesin family member 18B (KIF18B) expression. According to asarcoma detection product, the sarcoma detection product includes a reagent for detecting KIF18B expression, and is a product used for sarcoma diagnosis, radiotherapy means therapeutic effect evaluation and prognosis judgment. According to the diagnostic marker, genes significantly differential in carcinoma and para-carcinoma tissues in all sarcoma subtypes are widely screened, and are intersected with differentially expressed genes (DEGs) in carcinoma and para-carcinoma tissues of soft tissue sarcoma in a The Cancer Genome Atlas (TCGA) database, and it is the first time to discover that thegenes can be used as targets in all subtypes of sarcomas so as to improve huge differences of treatment schemes for patients with different subtypes of sarcomas at present; and the radiotherapy resistance-related gene KIF18B is obtained by further screening, which proves that the radiotherapy sensitivity of sarcoma cells can be enhanced by inhibiting the KIF18B, and the KIF18B can be used as a specific target for sarcoma radiotherapy. According to the diagnostic marker, by taking the KIF18 as the biomarker and with a targeting therapy, a new thought is provided for sarcoma treatment, and detection indexes are also provided for radiotherapy means therapeutic effect evaluation and prognosis judgment, and the diagnostic marker has important clinical application value.

Description

technical field [0001] The invention belongs to the field of molecular biology, relates to a marker related to sarcoma, in particular to a diagnostic marker related to radiotherapy resistance of sarcoma and its application. Background technique [0002] Sarcomas of mesenchymal origin are rare heterogeneous cancers with more than 100 different subtypes, affecting about 80% of soft tissues and 20% of bones. Currently, the main treatments for sarcomas are through surgery and radiotherapy. Although sarcomas are sometimes erroneously referred to as "radiation resistant," radiation therapy can reduce symptoms in metastatic patients, such as pain from bone metastases and hemoptysis from lung metastases. Image-guided radiation therapy may be an alternative to surgery for patients with low-metastatic sarcomas. Therefore, radiation therapy is an important means of sarcoma treatment. Although the incidence of sarcoma is relatively low, as one of the few clinical tumor models for neoa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574G01N33/68C12Q1/02A61K45/00A61P35/00A61K31/713A61K31/7105
CPCC12Q1/6886G01N33/57407G01N33/57484G01N33/6854G01N33/5011G01N33/5044A61K45/00A61P35/00A61K31/713A61K31/7105C12Q2600/158C12Q2600/118G01N2800/52G01N2500/10
Inventor 魏敏杰于兆进刘雯思
Owner 中国医科大学
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