CN117230190A - Biomarker H3C11 for rectal cancer curative effect and/or prognosis and application thereof - Google Patents
Biomarker H3C11 for rectal cancer curative effect and/or prognosis and application thereof Download PDFInfo
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- CN117230190A CN117230190A CN202310961048.8A CN202310961048A CN117230190A CN 117230190 A CN117230190 A CN 117230190A CN 202310961048 A CN202310961048 A CN 202310961048A CN 117230190 A CN117230190 A CN 117230190A
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- 238000004393 prognosis Methods 0.000 title claims abstract description 32
- 239000000090 biomarker Substances 0.000 title claims abstract description 31
- 208000015634 Rectal Neoplasms Diseases 0.000 title claims abstract description 24
- 206010038038 rectal cancer Diseases 0.000 title claims abstract description 24
- 201000001275 rectum cancer Diseases 0.000 title claims abstract description 24
- 230000000694 effects Effects 0.000 title claims abstract description 13
- 230000014509 gene expression Effects 0.000 claims abstract description 34
- 238000001959 radiotherapy Methods 0.000 claims abstract description 31
- 239000000523 sample Substances 0.000 claims description 13
- 210000001808 exosome Anatomy 0.000 claims description 9
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- 108090000623 proteins and genes Proteins 0.000 claims description 7
- 238000012360 testing method Methods 0.000 claims description 6
- 238000012163 sequencing technique Methods 0.000 claims description 5
- 210000001519 tissue Anatomy 0.000 claims description 5
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- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 108020004999 messenger RNA Proteins 0.000 claims description 2
- 210000004180 plasmocyte Anatomy 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 210000002966 serum Anatomy 0.000 claims description 2
- 210000004881 tumor cell Anatomy 0.000 claims description 2
- 230000004907 flux Effects 0.000 claims 1
- 230000035945 sensitivity Effects 0.000 description 8
- 230000005855 radiation Effects 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 238000011249 preoperative chemoradiotherapy Methods 0.000 description 3
- 238000003559 RNA-seq method Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
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- 102100025222 CD63 antigen Human genes 0.000 description 1
- 102000034342 Calnexin Human genes 0.000 description 1
- 108010056891 Calnexin Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
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Abstract
The invention relates to a biomarker H3C11 for treating and/or prognosis of rectal cancer and application thereof, and provides application of the biomarker H3C11 in preparation of products for predicting the treating and/or prognosis of rectal cancer, and whether the treating and/or prognosis of a subject receiving radiotherapy is good or not can be predicted by detecting the expression level of the biomarker. And, the predictive ability of the biomarker was verified in an external database. The biomarker H3C11 provided by the invention has good clinical application prospect in the aspect of predicting the curative effect and/or prognosis of the rectal cancer radiotherapy.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a biomarker H3C11 for rectal cancer curative effect and/or prognosis and application thereof.
Background
Of the patients with rectal cancer, 70% of non-metastatic patients are locally middle and late stage, requiring preoperative chemoradiotherapy combined surgery. How to predict the curative effect of preoperative radiotherapy and chemotherapy, avoid patients with radiotherapy resistance from receiving unnecessary radiotherapy and chemotherapy, or help patients with radiotherapy sensitivity to obtain better curative effect, even avoid surgery and obtain opportunities of reserving anus, is a significant topic.
At present, the sensitivity of preoperative chemoradiotherapy is judged clinically mainly by multi-disciplinary comprehensive judgment based on accurate images, including digital rectal examination, enteroscopy, high-resolution nuclear magnetic resonance examination (MRI) and local biopsy pathology, but the misjudgment rate still can reach 20-30%. If a molecular marker which is more suitable and can be widely applied can be found to predict the sensitivity of radiotherapy, the personalized treatment of patients can be effectively promoted, the survival is improved, the prognosis of the patients is improved, and the medical resources which are short of the country are saved.
In the prior art, molecular markers for predicting radiation sensitivity are mostly obtained through tissue sequencing screening. However, in clinical applications, patients are predicted to be therapeutically effective by invasive procedures, and patient acceptance is poor. Those skilled in the art would like to develop new molecular markers more suitable for clinical applications.
Disclosure of Invention
The invention aims to provide a biomarker H3C11 for treating and/or prognosis of rectal cancer and application thereof, and the therapeutic effect and/or prognosis of the subject receiving radiotherapy can be predicted by detecting the expression level of H3C11 so as to assist clinical diagnosis and treatment.
To this end, in a first aspect, the invention provides the use of a biomarker, H3C11, in the manufacture of a product for predicting the efficacy and/or prognosis of rectal cancer.
In some embodiments, the efficacy and prognosis refer to the efficacy and prognosis of radiation therapy, respectively.
In some embodiments, the product that predicts the efficacy and/or prognosis of rectal cancer comprises a product that detects the expression level of the biomarker.
In some embodiments, the expression level refers to mRNA expression level and/or protein expression level of the biomarker.
In some embodiments, the sample to be tested for detecting the expression level of the biomarker is a tissue sample or fluid from a subject.
In some embodiments, the subject is a patient with colorectal cancer.
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.
In some embodiments, the test sample for detecting the expression level of the biomarker is a plasma exosome from the subject.
In some embodiments, if the expression level of the biomarker in the test sample is above a threshold, the subject is predicted to be susceptible to radiation therapy, i.e., the subject is predicted to have a good efficacy and/or prognosis for receiving radiation therapy; and if the expression level of the biomarker in the biological sample to be tested is lower than a threshold value, predicting that the subject is insensitive to radiotherapy, i.e. predicting that the subject has poor curative effect and/or prognosis in receiving radiotherapy.
In some embodiments, if the expression level TPM value of the biomarker is higher than 250 in the sample to be tested, the subject is predicted to be sensitive to radiation therapy, i.e., the subject is predicted to have a good therapeutic effect and/or prognosis for receiving radiation therapy; if the expression level TPM value of the biomarker in the biological sample to be tested is lower than 250, the subject is predicted to be insensitive to radiotherapy, i.e. the subject is predicted to have poor curative effect and/or prognosis when receiving radiotherapy.
As known to those skilled in the art, the gene expression level TPM is a term in the field of genomics. The TPM is all referred to as "transcripts per million", the number of gene transcripts per million sequencing reads (reads). The calculation method of the gene expression quantity TPM is to divide the number of transcripts of a target gene by the total RNA sequencing reading and multiply the total RNA sequencing reading by one million to obtain the number of transcripts of the gene in each million sequencing readings.
In some embodiments, the product that predicts the efficacy and/or prognosis of rectal cancer is selected from the group consisting of: reagents, kits, test papers, gene chips, high throughput sequencing platforms, antibody chips, instrument platforms, and the like.
In some embodiments, the instrument platform comprises a measurement module for measuring the expression level of the biomarker in the test sample.
Compared with the prior art, the invention has the following beneficial effects:
currently, there is no major breakthrough in international research on molecular markers of sensitivity to radiotherapy of rectal cancer, and no reliable prediction tool is currently available. In the study of the present invention, it was found that the expression level of H3C11 in plasma exosomes was significantly different in patients in the radiation-sensitive and resistant groups, and also verified in the TCGA database. The invention provides application of a biomarker H3C11 in preparing a product for predicting the curative effect and/or prognosis of rectal cancer, and has good clinical application prospect.
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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 drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention. In the drawings:
fig. 1: according to some embodiments of the invention, the extracted exosomes are identified;
a: exosome particle size distribution map; b: imaging results by a transmission electron microscope; c: the result of western blot detection of the positive marker CD9/Alix/CD63 and the negative marker Calnexin in the exosomes;
fig. 2: according to some embodiments of the invention, the overall survival of H3C11 high expressing group patients and H3C11 low expressing group patients is analyzed.
Detailed Description
Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.
Example 1
15 patients with locally advanced rectal cancer were enrolled, 8 of which reached complete remission of the pathology after receiving neoadjuvant radiation therapy and had a good prognosis (radiation sensitive group), and 7 reached incomplete remission of the pathology and had a poor prognosis (radiation resistant group). Baseline plasma of the above patients was obtained, plasma exosomes were extracted, and the accuracy of the extracted plasma exosomes was identified using nanoparticle tracking analysis and transmission electron microscopy, and the results are shown in fig. 1.
The plasma exosomes of the two groups of patients were subjected to full transcriptome sequencing analysis, and differentially expressed mirnas, lncrnas and mrnas were found. Wherein, the expression of H3C11 in the radiotherapy sensitive group is obviously higher than that in the radiotherapy resistant group, the average value of log2FC is-0.8074, and the median value of log2FC is-1.2798. The efficacy and prognosis of patients with rectal cancer after receiving radiation therapy are predicted according to the following method: taking TPM value 250 as an H3C11 gene expression quantity threshold value, judging that the radiotherapy is sensitive if the TPM value is higher than the threshold value, and predicting that the TPM value has good curative effect and prognosis after receiving the radiotherapy; if the radiation therapy is lower than the threshold, the radiation therapy is not sensitive, and the curative effect and prognosis after the radiation therapy is received are predicted to be poor. The prediction of the 15 patients with advanced rectal cancer was performed according to the above method, and the AUC value of the predictive ability of H3C11 for radiation sensitivity was 0.8036.
The results show that the H3C11 has good application prospect in the aspect of predicting the curative effect and prognosis of the patient with the rectal cancer after receiving radiotherapy.
Example 2
To further verify the predictive ability of H3C11 for radiation sensitivity in patients with rectal cancer, 166 patients with rectal cancer receiving radiation therapy were selected from the TCGA database, and the total survival probability of the two groups of high expression and low expression was analyzed according to the H3C11 gene expression level, and the results are shown in FIG. 2.
From fig. 2, the overall survival rate of patients with low H3C11 expression is significantly worse than that of patients with high H3C11 expression, verifying that H3C11 has a good predictive power for radiation sensitivity in patients with rectal cancer.
The present invention is not limited to the above-mentioned embodiments, and any changes or substitutions that can be easily understood by those skilled in the art within the technical scope of the present invention are intended to be included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. Use of a biomarker in the manufacture of a product for predicting the efficacy and/or prognosis of rectal cancer, characterized in that the biomarker is H3C11.
2. The use according to claim 1, wherein the efficacy and prognosis refer to the efficacy and prognosis of radiotherapy, respectively.
3. The use according to claim 1, wherein the product for predicting the efficacy and/or prognosis of rectal cancer comprises a product for detecting the expression level of the biomarker.
4. The use according to claim 3, wherein the expression level refers to mRNA expression level and/or protein expression level of the biomarker.
5. The use according to claim 3, wherein the sample to be tested for detecting the expression level of the biomarker is a tissue sample or fluid from a subject;
preferably, 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.
6. The use according to claim 3, wherein the sample to be tested for detecting the expression level of the biomarker is plasma exosomes from the subject.
7. The use according to any one of claims 3 to 6, wherein the subject is a patient with rectal cancer.
8. The use of claim 3, wherein if the expression level of the biomarker in the test sample is above a threshold, the subject is predicted to have a good efficacy and/or prognosis for receiving radiation therapy; if the expression level of the biomarker in the biological sample to be tested is lower than a threshold value, the subject is predicted to have poor curative effect and/or prognosis when receiving radiotherapy.
9. The use according to claim 1, wherein the product for predicting the efficacy and/or prognosis of rectal cancer is selected from any one of the following groups: reagent, kit, test paper, gene chip, high flux sequencing platform, antibody chip and instrument platform.
10. The use according to claim 9, wherein the instrument platform comprises a measurement module for measuring the expression level of the biomarker in the sample to be tested.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310961048.8A CN117230190A (en) | 2023-08-01 | 2023-08-01 | Biomarker H3C11 for rectal cancer curative effect and/or prognosis and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310961048.8A CN117230190A (en) | 2023-08-01 | 2023-08-01 | Biomarker H3C11 for rectal cancer curative effect and/or prognosis and application thereof |
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| CN117230190A true CN117230190A (en) | 2023-12-15 |
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| CN202310961048.8A Pending CN117230190A (en) | 2023-08-01 | 2023-08-01 | Biomarker H3C11 for rectal cancer curative effect and/or prognosis and application thereof |
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| CN (1) | CN117230190A (en) |
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2023
- 2023-08-01 CN CN202310961048.8A patent/CN117230190A/en active Pending
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