Application of hsa-miR-92b-5p as a radiotherapy sensitivity marker for low-grade glioma

Abstract

This invention discloses the application of hsa-miR-92b-5p as a biomarker for radiosensitivity in low-grade gliomas. The inventors found that high expression of hsa-miR-92b-5p indicates radioresistance in patients with low-grade gliomas, a high risk of recurrence after radiotherapy, and a poor prognosis. hsa-miR-92b-5p can serve as a biomarker for radioresistance in low-grade gliomas, enabling personalized radiotherapy for these tumors, improving treatment efficacy, and avoiding ineffective treatment.

Description

Technical Field

[0001] This invention belongs to the field of diagnostics, specifically relating to the application of hsa-miR-92b-5p as a radiosensitivity marker for low-grade gliomas. Background Technology

[0002] Low-grade gliomas refer to gliomas classified below grade II in the World Health Organization's classification of tumors of the central nervous system. They include three main pathological types: diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. Compared to other high-grade gliomas, low-grade gliomas are relatively less malignant and have a better prognosis. Nevertheless, as a relatively common primary malignant intracranial tumor, low-grade gliomas still pose a significant threat to public health. Surgical treatment is currently the main radical cure for low-grade gliomas. However, due to their unique anatomical location and invasive growth characteristics, complete tumor resection is often difficult to guarantee, resulting in a high risk of postoperative recurrence for patients with low-grade gliomas. Radiotherapy is an important adjuvant therapy to reduce postoperative recurrence of low-grade gliomas, and a considerable number of patients require adjuvant radiotherapy to improve prognosis. However, gliomas exhibit significant differences in their sensitivity to radiation. In some patients, tumor cells are relatively resistant to radiation, and conventional radiotherapy doses may not completely kill the tumor cells, leading to tumor residue and recurrence, thus affecting the effectiveness of radiotherapy for gliomas. Therefore, identifying radiosensitivity markers for low-grade gliomas is of great significance for guiding individualized treatment of low-grade gliomas.

[0003] MicroRNAs (miRNAs) are a class of single-stranded non-coding RNA molecules, approximately 22 nucleotides in length. They can mediate mRNA degradation or inhibit translation by binding to specific mRNA sequences, thereby exerting post-transcriptional regulatory effects on gene expression. miRNAs play important regulatory roles in organismal development and disease progression. Current research suggests that aberrant miRNA expression is closely related to the development and progression of malignant tumors, including low-grade gliomas. Furthermore, using aberrant miRNA expression levels as biomarkers has great potential for application in helping to identify biological behaviors related to malignant tumors.

[0004] hsa-miR-92b-5p is a miRNA gene located on chromosome 1. Previous studies have reported aberrant expression of hsa-miR-92b-5p in various malignant tumors and its potential role in regulating tumor development. However, there is currently no evidence linking hsa-miR-92b-5p to radioresistance in malignant tumors. Summary of the Invention

[0005] The purpose of this invention is to overcome at least one deficiency of the prior art and to provide hsa-miR-92b-5p as a radiosensitivity marker for low-grade gliomas.

[0006] The technical solution adopted in this invention is:

[0007] The first aspect of the present invention provides:

[0008] Application of reagents for quantifying hsa-miR-92b-5p in the preparation of reagents for assessing the sensitivity of tumors to radiotherapy.

[0009] In some applications, the tumor is a low-grade glioma.

[0010] In some application examples, reagents for quantifying hsa-miR-92b-5p are selected from high-throughput miRNA sequencing, miRNA microarrays, real-time quantitative qPCR kits for detecting hsa-miR-92b-5p expression levels, or specific hsa-miR-92b-5p in situ hybridization kits.

[0011] In some applications, the reagents used to quantify hsa-miR-92b-5p are used to detect tissue samples.

[0012] A second aspect of the present invention provides:

[0013] A system for determining the sensitivity of a tumor to radiotherapy, comprising:

[0014] hsa-miR-92b-5p quantification device: used to quantify the amount or concentration of hsa-miR-92b-5p in a sample;

[0015] Assessment device: Determines the sensitivity of tumors to radiotherapy based on the amount or concentration of hsa-miR-92b-5p in the sample;

[0016] Result output device: Outputs the result given by the judgment device.

[0017] In some system instances, the sample is a tissue sample.

[0018] In some systemic instances, the tumor is a low-grade glioma.

[0019] In some system examples, the hsa-miR-92b-5p quantification device is selected from high-throughput miRNA sequencing, miRNA microarrays, real-time quantitative qPCR kits for detecting hsa-miR-92b-5p expression levels, or specific hsa-miR-92b-5p in situ hybridization kits.

[0020] In some systematic instances, the criteria for judging sensitivity are as follows: when detecting hsa-miR-92b-5p in situ hybridization, if the proportion of strongly stained cells is greater than 50%, it is determined that hsa-miR-92b-5p is highly expressed, the tumor is less sensitive to radiotherapy, and the risk of recurrence after radiotherapy is high; conversely, if the proportion of strongly stained cells is greater than 50%, it is determined that hsa-miR-92b-5p is low expressed, the tumor is more sensitive to radiotherapy, and the risk of recurrence after radiotherapy is relatively low.

[0021] The beneficial effects of this invention are:

[0022] The inventors' research found that high expression of hsa-miR-92b-5p indicates radioresistance in patients with low-grade gliomas, leading to a high risk of recurrence after radiotherapy and a poor prognosis. hsa-miR-92b-5p can serve as a marker of radioresistance in low-grade gliomas, enabling personalized radiotherapy for these tumors, improving treatment efficacy, and avoiding ineffective treatment. Attached Figure Description

[0023] Figure 1 This analysis presents the association between high hsa-miR-92b-5p expression and radiosensitivity in low-grade gliomas. In patients with low-grade gliomas who received radiotherapy, high hsa-miR-92b-5p expression indicated a higher risk of recurrence and a shorter median survival. In patients with low-grade gliomas who did not receive radiotherapy, hsa-miR-92b-5p expression levels were not significantly correlated with recurrence risk or survival.

[0024] Figure 2 The time-dependent ROC curves of hsa-miR-92b-5p expression levels predicting mortality and tumor progression within one year in patients with low-grade gliomas receiving radiotherapy are presented. The results suggest that hsa-miR-92b-5p has good predictive efficacy. Detailed Implementation

[0025] The first aspect of the present invention provides:

[0026] Application of reagents for quantifying hsa-miR-92b-5p in the preparation of reagents for assessing the sensitivity of tumors to radiotherapy.

[0027] In some applications, the tumor is a low-grade glioma. Experimental data suggests that it is more valuable in identifying low-grade gliomas.

[0028] The reagents for quantifying hsa-miR-92b-5p can be miRNA quantification reagents. In some application examples, the reagents for quantifying hsa-miR-92b-5p are selected from high-throughput miRNA sequencing, miRNA microarrays, real-time quantitative qPCR kits for detecting hsa-miR-92b-5p expression levels, or specific hsa-miR-92b-5p in situ hybridization kits.

[0029] In some applications, the reagents used to quantify hsa-miR-92b-5p are used to detect tissue samples.

[0030] A second aspect of the present invention provides:

[0031] A system for determining the sensitivity of a tumor to radiotherapy, comprising:

[0032] hsa-miR-92b-5p quantification device: used to quantify the amount or concentration of hsa-miR-92b-5p in a sample;

[0033] Assessment device: Determines the sensitivity of tumors to radiotherapy based on the amount or concentration of hsa-miR-92b-5p in the sample;

[0034] Result output device: Outputs the result given by the judgment device.

[0035] In some system instances, the sample is a tissue sample.

[0036] In some systematic instances, the tumor was a low-grade glioma. Experimental data suggests that it is more valuable in diagnosing low-grade gliomas.

[0037] In some system examples, the hsa-miR-92b-5p quantification device is selected from high-throughput miRNA sequencing, miRNA microarrays, real-time quantitative qPCR kits for detecting hsa-miR-92b-5p expression levels, or specific hsa-miR-92b-5p in situ hybridization kits.

[0038] Sensitivity assessment can be based on existing data analysis, such as ROC curve analysis. The criteria vary depending on the quantitative method used. In some systematic examples, the sensitivity assessment criteria are as follows: when detecting hsa-miR-92b-5p in situ hybridization, if the proportion of strongly stained cells is greater than 50%, it is considered that hsa-miR-92b-5p expression is high, indicating low sensitivity to tumor radiotherapy and a high risk of recurrence after radiotherapy; conversely, if the proportion of strongly stained cells is greater than 50%, it is considered that hsa-miR-92b-5p expression is low, indicating high sensitivity to tumor radiotherapy and a relatively low risk of recurrence after radiotherapy.

[0039] The technical solution of the present invention will be further explained below with reference to experiments.

[0040] The expression of hsa-miR-92b-5p and the discovery of tumor radiosensitivity

[0041] Clinical data and miRNA sequencing data for low-grade gliomas (LGGs) were downloaded from The Cancer Genome Atlas (TCGA) database (portal.gdc.cancer.gov, database updated as of May 3, 2022). A total of 506 LGG cases were included, of which 300 received postoperative radiotherapy, 176 did not, and the radiotherapy status was unclear in 30 cases. Of these, 476 LGG cases with clear radiotherapy status were retained for further analysis.

[0042] The downloaded miRNA sequencing data were normalized to RPM (Reads per Million mapped reads) format using R (version 3.6.3) and corresponding R packages, and the expression information of hsa-miR-92b-5p was extracted. For patients with low-grade gliomas who received and did not receive radiotherapy, the overall survival curve and progression-free survival curve were statistically analyzed using the Kaplan-Meier method and log-rank test based on the expression level of hsa-miR-92b-5p. The method that yielded the minimum required results was then used. P We used the hsa-miR-92b-5p expression level as the cutoff value for high and low expression to compare the prognostic differences between low-grade glioma patients who received and did not receive radiotherapy. For low-grade glioma patients, radioresistance is closely related to post-radiotherapy recurrence. Our results showed that high hsa-miR-92b-5p expression was positively correlated with the risk of post-radiotherapy recurrence in low-grade glioma patients who received postoperative radiotherapy, but had no significant predictive value in patients who underwent surgery alone. Figure 1 As shown, in patients with low-grade gliomas who received radiotherapy, those with high expression of hsa-miR-92b-5p in their tumor tissue had significantly lower overall survival (5-year survival rate: 45.8±5.9% vs. 64.1±6.9%) and progression-free survival (5-year progression-free survival rate: 24.1±5.5% vs. 56.6±6.6%) compared to those with low expression of hsa-miR-92b-5p; however, this result had no significant predictive value in patients with low-grade gliomas who underwent surgery alone. These results suggest that high expression of miR-92b-5p is associated with tumor radioresistance in patients with low-grade gliomas.

[0043] Further, for patients with low-grade gliomas receiving radiotherapy, ROC curves were plotted using the timeROC package to analyze the predictive efficacy of miR-92b-5p expression levels for radioresistance in these patients. Figure 2 As shown, hsa-miR-92b-5p expression has a high predictive power for tumor progression and death within one year in patients receiving radiotherapy, indicating that hsa-miR-92b-5p can serve as a predictive biomarker for radioresistance in low-grade gliomas.

[0044] The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions without departing from the concept of the present invention are all within the protection scope of the present invention.

Claims

1. Application of reagent for quantifying hsa-miR-92b-5p in the preparation of reagent for assessing the sensitivity of tumors to radiotherapy, wherein the tumor is a low-grade glioma, and the sample tested by the reagent for quantifying hsa-miR-92b-5p is a tissue sample.

2. The application according to claim 1, characterized in that, The reagents for quantifying hsa-miR-92b-5p are selected from high-throughput miRNA sequencing, miRNA microarrays, real-time quantitative qPCR kits for detecting hsa-miR-92b-5p expression levels, or specific hsa-miR-92b-5p in situ hybridization kits.

3. A system for determining the radiotherapy sensitivity of a tumor, said tumor being a low-grade glioma, comprising: hsa-miR-92b-5p quantification device: used to quantify the amount or concentration of hsa-miR-92b-5p in a sample, wherein the sample is a tissue sample; Assessment device: Determines the sensitivity of tumors to radiotherapy based on the amount or concentration of hsa-miR-92b-5p in the sample; Result output device: Outputs the result given by the judgment device.

4. The system according to claim 3, characterized in that, The hsa-miR-92b-5p quantification device is selected from high-throughput miRNA sequencing, miRNA microarray, real-time quantitative qPCR kit for detecting hsa-miR-92b-5p expression level, or specific hsa-miR-92b-5p in situ hybridization kit.

5. The system according to claim 3, characterized in that, The criteria for judging sensitivity are as follows: when detecting hsa-miR-92b-5p in situ hybridization, if the proportion of strongly stained cells is greater than 50%, it is determined that hsa-miR-92b-5p is highly expressed, the tumor is less sensitive to radiotherapy, and the risk of recurrence after radiotherapy is high; conversely, if the proportion of strongly stained cells is greater than 50%, it is determined that hsa-miR-92b-5p is low expressed, the tumor is more sensitive to radiotherapy, and the risk of recurrence after radiotherapy is relatively low.

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