Biomarker h3c11 for efficacy and / or prognosis of rectal cancer and use thereof

Abstract

The present application relates to the biological marker H3C11 for predicting the curative effect and / or prognosis of rectal cancer and its application, and provides the use of the biological marker H3C11 in the preparation of products for predicting the curative effect and / or prognosis of rectal cancer, and the expression level of the biological marker can be detected to predict whether the curative effect and / or prognosis of radiotherapy for a subject is good. Moreover, the prediction ability of the biological marker is verified in an external database. The biological marker H3C11 provided by the present application has a good clinical application prospect in predicting the curative effect and / or prognosis of radiotherapy for rectal cancer.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a biomarker H3C11 for curative effect and / or prognosis of rectal cancer and application thereof. BACKGROUND

[0002] In patients with rectal cancer, 70% of non-metastatic patients are in local intermediate and advanced stages, and need to be treated by preoperative radiotherapy combined with surgery. How to predict the curative effect of preoperative radiotherapy, avoid unnecessary radiotherapy for patients with radiotherapy resistance, or help patients with radiotherapy sensitivity to obtain better curative effect and even avoid surgery and get the opportunity to retain the anus, is a significant issue.

[0003] At present, the main clinical method is to make a comprehensive judgment based on precise imaging, including rectal examination, enteroscopy, high-resolution magnetic resonance examination (MRI) and local biopsy pathology to judge the sensitivity of preoperative radiotherapy, but the misjudgment rate can still reach 20-30%. If a more suitable and widely applicable molecular marker can be found to predict radiotherapy sensitivity, it will effectively promote individualized treatment of patients, improve survival and improve the prognosis of patients, and save the country's scarce medical resources.

[0004] In the prior art, molecular markers for predicting radiotherapy sensitivity are mostly obtained by tissue sequencing screening. However, in clinical application, the curative effect of patients is predicted by invasive operation, and the patient's acceptance is poor. The skilled person in the art hopes to develop a new molecular marker more suitable for clinical application. SUMMARY

[0005] The purpose of the present application is to provide a biomarker H3C11 for curative effect and / or prognosis of rectal cancer and application thereof. By detecting the expression level of H3C11, the curative effect and / or prognosis of radiotherapy of the subject can be predicted to assist clinical diagnosis and treatment.

[0006] To this end, in a first aspect, the present application provides a use of a biomarker in the preparation of a product for predicting curative effect and / or prognosis of rectal cancer, wherein the biomarker is H3C11.

[0007] In some embodiments, the curative effect and prognosis refer to the curative effect and prognosis of radiotherapy, respectively.

[0008] In some embodiments, the product for predicting curative effect and / or prognosis of rectal cancer comprises a product for detecting the expression level of the biomarker.

[0009] In some embodiments, the expression level refers to the mRNA expression level and / or protein expression level of the biomarker.

[0010] In some embodiments, the sample to be tested for detecting the expression level of the biomarker is a tissue sample or a fluid from the subject.

[0011] In some embodiments, the subject is a colorectal cancer patient.

[0012] In some embodiments, the sample to be tested for detecting the expression level of the biomarker is at least one of tumor tissue, tumor cells, blood, plasma and serum from the subject.

[0013] In some embodiments, the sample to be tested for detecting the expression level of the biomarker is plasma exosome from the subject.

[0014] In some embodiments, if the expression level of the biomarker in the sample to be tested is higher than a threshold value, it is predicted that the subject is sensitive to radiotherapy, i.e. it is predicted that the subject has a good curative effect and / or prognosis after receiving radiotherapy; if the expression level of the biomarker in the sample to be tested is lower than a threshold value, it is predicted that the subject is not sensitive to radiotherapy, i.e. it is predicted that the subject has a poor curative effect and / or prognosis after receiving radiotherapy.

[0015] In some embodiments, if the expression level of the biomarker in the sample to be tested is higher than a threshold value, it is predicted that the subject is sensitive to radiotherapy, i.e. it is predicted that the subject has a good curative effect and / or prognosis after receiving radiotherapy; if the expression level of the biomarker in the sample to be tested is lower than a threshold value, it is predicted that the subject is not sensitive to radiotherapy, i.e. it is predicted that the subject has a poor curative effect and / or prognosis after receiving radiotherapy.

[0016] As known by those skilled in the art, the gene expression level TPM is a term in the field of genomics. TPM stands for "transcripts per million", i.e. the number of gene transcripts per million sequencing reads. The calculation method of the gene expression level TPM is to divide the number of transcripts of the target gene by the total RNA sequencing reads, and then multiply by one million, i.e. the number of transcripts of the gene per million sequencing reads.

[0017] In some embodiments, the product for predicting the curative effect and / or prognosis of colorectal cancer is selected from the group consisting of reagents, kits, test papers, gene chips, high-throughput sequencing platforms, antibody chips, instrument platforms, etc.

[0018] In some embodiments, the instrument platform comprises a measurement module for measuring the expression level of the biomarker in the sample to be tested.

[0019] Compared with the prior art, the present application has the following beneficial effects:

[0020] Currently, there is no significant breakthrough in the international research on molecular markers of radiotherapy sensitivity of rectal cancer, and there is still a lack of reliable prediction tools. In the research of the present application, it is found that the expression amount of H3C11 in plasma exosomes is significantly different between patients in radiotherapy sensitive and resistant groups, and it is also verified in the TCGA database. The present application provides the use of the biomarker H3C11 in preparing a product for predicting the efficacy and / or prognosis of rectal cancer, which has good clinical application prospects. BRIEF DESCRIPTION OF DRAWINGS

[0021] Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The accompanying drawings are intended to further assist in understanding the preferred embodiments, and are not considered as limiting the application. In the drawings:

[0022] Figure 1 : According to some embodiments of the present application, the extracted exosomes are identified;

[0023] a: Exosome particle size distribution chart; b: Transmission electron microscopy imaging result; c: Western blot detection results of positive markers CD9 / Alix / CD63 and negative markers Calnexin in exosomes;

[0024] Figure 2 : According to some embodiments of the present application, the results of overall survival analysis of patients in the H3C11 high expression group and patients in the H3C11 low expression group. DETAILED DESCRIPTION

[0025] Exemplary embodiments of the present disclosure will be described in greater detail below with reference to the accompanying drawings. Although exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that the present disclosure can be more thoroughly understood and the scope of the present disclosure can be accurately conveyed to those skilled in the art.

[0026] Example 1

[0027] Fifteen patients with locally advanced rectal cancer were included, of which 8 patients achieved pathological complete remission after neoadjuvant radiotherapy and had good prognosis (radiotherapy sensitive group), and 7 patients achieved pathological incomplete remission and had poor prognosis (radiotherapy resistant group). The baseline plasma of the above patients was obtained, and the plasma exosomes were extracted. The accuracy of the extracted plasma exosomes was identified by nanoparticle tracking analysis and transmission electron microscopy, and the results are shown in Figure 1 .

[0028] The plasma exosomes of the two groups of patients are subjected to whole transcriptome sequencing analysis, and differentially expressed miRNAs, IncRNAs and mRNAs are found. Among them, the expression of H3C11 in the radiotherapy sensitive group is significantly higher than that in the radiotherapy resistant group, and the log2FC of the mean is -0.8074, and the log2FC of the median is -1.2798. The efficacy and prognosis of the patients with rectal cancer after radiotherapy are predicted according to the following method: taking TPM value 250 as the H3C11 gene expression threshold, if higher than the threshold, it is judged as radiotherapy sensitive, and it is predicted that it can have good efficacy and prognosis after radiotherapy; if lower than the threshold, it is judged as radiotherapy insensitive, and it is predicted that the efficacy and prognosis after radiotherapy are poor. According to the above method, the above 15 patients with advanced rectal cancer are predicted, and the AUC value of the prediction ability of H3C11 for radiotherapy sensitivity is 0.8036.

[0029] The above results show that H3C11 has good application prospects in predicting the efficacy and prognosis of rectal cancer patients after radiotherapy.

[0030] Example 2

[0031] In order to further verify the prediction ability of H3C11 for radiotherapy sensitivity of rectal cancer patients, 166 rectal cancer patients who received radiotherapy were selected from the TCGA database, and were divided into high expression group and low expression group according to the expression of H3C11 gene, and the overall survival probability of the high expression and low expression groups was analyzed, and the results are shown in Figure 2

[0032] According to Figure 2 It can be known that the overall survival rate of patients with low expression of H3C11 is significantly lower than that of patients with high expression of H3C11, which verifies that H3C11 has good prediction ability for the radiotherapy sensitivity of patients with rectal cancer.

[0033] The above is only a preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any person skilled in the art can easily think of changes or replacements within the technical range disclosed by the present application, which should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.​

Claims

1. The use of a formulation for detecting the expression level of a biomarker in the preparation of products for predicting the efficacy and / or prognosis of rectal cancer, characterized in that, The biomarker is H3C11; The efficacy and prognosis mentioned refer to the efficacy and prognosis of radiotherapy, respectively.

2. The use as described in claim 1, characterized in that, The expression level refers to the mRNA expression level and / or protein expression level of the biomarker.

3. The use as described in claim 1, characterized in that, The test sample used to detect the expression level of the biomarker is plasma exosomes from the subject.

4. The use as described in claim 3, characterized in that, The subjects were patients with rectal cancer.

5. The use as described in claim 3, characterized in that, If the expression level of the biomarker in the test sample is higher than the threshold, it is predicted that the subject will have good efficacy and / or prognosis after receiving radiotherapy; if the expression level of the biomarker in the test sample is lower than the threshold, it is predicted that the subject will have poor efficacy and / or prognosis after receiving radiotherapy.

6. The use as described in claim 1, characterized in that, The product used to predict the efficacy and / or prognosis of rectal cancer is selected from any one of the following groups: reagents, instrument platforms.

7. The use as described in claim 1, characterized in that, The product used to predict the efficacy and / or prognosis of rectal cancer is selected from any one of the following groups: kits, high-throughput sequencing platforms.

8. The use as described in claim 1, characterized in that, The product used to predict the efficacy and / or prognosis of rectal cancer is selected from any one of the following groups: test strips, gene chips, and antibody chips.

9. The use as described in claim 6, characterized in that, The instrument platform includes a measurement module for measuring the expression level of the biomarker in the sample to be tested.

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