A biomarker for radiotherapy sensitization and prognosis prediction of solid tumor and application thereof

Abstract

The application relates to a biomarker for radiotherapy synergism and prognosis prediction of a solid tumor and application thereof, and the biomarker is arginine and / or proline. Compared with the prior art, the specificity of the arginine and / or proline is better, and the application is simple. The arginine and / or proline can be detected in patient serum, the detection means is more economical and simple, has more opportunities to be applied to the clinic, and has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of biotechnology and relates to a biomarker for enhancing the efficacy of radiotherapy for solid tumors and predicting prognosis, and its application. Background Technology

[0002] Radiation therapy kills tumors and inhibits the progression of solid tumors by inducing apoptosis in tumor cells through DNA damage or inhibiting mitosis. It is an indispensable adjuvant therapy in clinical cancer treatment. For example, adjuvant radiotherapy is included in the treatment regimens for all subtypes of breast cancer, which can not only significantly reduce the recurrence rate of breast cancer, but also improve the survival rate of early and some advanced breast cancers. Surgical resection of the tumor followed by TMZ chemotherapy and adjuvant radiotherapy has been the standard treatment for glioblastoma. However, multiple studies have shown that irradiation can induce global changes in the tumor microenvironment, such as changes in the immune system and tumor microvessels, which can lead to tumor recurrence and radiation resistance. The effectiveness of irradiation, the persistence of the response, and tolerability are the main challenges to achieving ideal irradiation results. Currently, there are no good drug targets in clinical practice to effectively improve the radiotherapy tolerance of tumor cells, and there is an urgent need for a new sensitizing target for solid tumor irradiation.

[0003] While radiotherapy has improved mortality rates for most cancers, current methods for determining whether breast cancer patients are suitable for radiation therapy and predicting its potential side effects are quite limited. Various biomarkers have become indispensable methods for assisting in the early diagnosis, prognosis assessment, and prediction of potential toxic side effects in breast cancer patients. For example, the frequency of BRCA1 / BRCA2 gene mutations can be used to assess the genetic risk of breast cancer, and overexpression of the HER2 molecule is associated with shorter recurrence time and a significantly reduced overall survival in breast cancer patients. However, these detection methods are relatively complex and only cover part of the predictive needs. There is an urgent need for a more cost-effective and convenient biomarker detection method for predicting the efficacy of breast cancer radiotherapy. Summary of the Invention

[0004] The purpose of this invention is to provide a biomarker for enhancing the efficacy of radiotherapy for solid tumors and predicting prognosis, and its application.

[0005] The objective of this invention can be achieved through the following technical solutions: One of the technical solutions of the present invention is to provide a biomarker for enhancing the radiotherapy efficacy of solid tumors in the preparation of products for improving the radiotherapy sensitivity of solid tumors, wherein the biomarker for enhancing the radiotherapy efficacy of solid tumors is arginine and / or proline.

[0006] In some specific embodiments, the solid tumor includes breast cancer and glioma.

[0007] The second technical solution of the present invention is to provide a product for improving the radiosensitivity of solid tumors, the product comprising arginine inhibitors and / or proline supplements.

[0008] In some specific embodiments, the arginine inhibitor and / or proline supplement is a formulation for reducing tumor volume.

[0009] In some specific embodiments, the product is a reagent or a kit.

[0010] The third technical solution of the present invention is to provide a biomarker for predicting the prognosis of solid tumors in the preparation of a detection product for predicting the prognosis and efficacy of solid tumors, wherein the biomarker for predicting the prognosis of solid tumors is arginine and / or proline.

[0011] In some specific implementations, the prognostic measure is radiotherapy.

[0012] In some specific embodiments, the solid tumor includes breast cancer and glioma.

[0013] In some specific embodiments, the detection product is a reagent, kit, test strip, or chip.

[0014] The fourth technical solution of the present invention is to provide a detection product for predicting the prognosis and efficacy of solid tumors, including reagents for detecting the content of arginine and / or proline.

[0015] In some specific embodiments, the prognostic criteria for solid tumors are as follows: the arginine expression level in solid tumors after prognosis is higher than that before prognosis, indicating a poor prognosis. And / or, lower proline expression levels in solid tumors after prognosis compared to before prognosis indicate a poor prognosis. Compared with the prior art, the present invention has the following advantages: The biomarkers arginine and proline of this invention have a wider range of indications, better specificity, and are simpler to use than traditional treatment methods. Compared with traditional methods of detecting gene mutation frequency, they can be detected in patient serum, making the detection method more economical and convenient, and more likely to be applied in clinical practice, thus showing good application prospects. Attached Figure Description

[0016] Figure 1 The levels of arginine and proline in serum samples before and after irradiation in glioma and breast cancer patients (n=12).

[0017] Figure 2 To detect changes in the volume of in situ breast cancer tumors before and after the application of arginine and proline, as well as before and after irradiation, in small animal tumor tissues.

[0018] Figure 3Statistical graph showing changes in the volume of in situ breast cancer tumors before and after the application of arginine and proline, and before and after irradiation, in small animal tumor tissues.

[0019] Figure 4 To detect changes in in situ tumor volume of gliomas before and after the application of arginine and proline, as well as before and after irradiation, using magnetic resonance imaging.

[0020] Figure 5 A statistical graph showing the changes in in situ tumor volume of gliomas before and after the application of arginine and proline, and before and after irradiation, as detected by magnetic resonance imaging.

[0021] Figure 6 The values ​​of arginine and proline in serum samples of mice with gliomas and breast cancers before and after arginine and proline supplementation and before and after irradiation.

[0022] All results were compared and statistically analyzed between groups using GrphaPad software. Detailed Implementation

[0023] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0025] Example 1: 1. Construction of an orthotopic animal model of glioma: The murine glioma cell line GL261 was cultured in TC-treated T225 flasks to 50%-60% confluence. The culture medium was discarded, and the cells were washed once with PBS. 4 mL of trypsin was added to digest the glioma cells into single cells. 8 mL of complete culture medium was added to neutralize the trypsin, and the cells were transferred to a 15 mL centrifuge tube. Microscopic examination confirmed that no cells remained at the bottom of the flask. The cells were centrifuged at 1000 rpm for 5 min. The supernatant was discarded, and 10 mL of pure DMEM was added to resuspend the cells. The cells were centrifuged at 1000 rpm for 5 min, and this step was repeated 4 times to remove residual FBS on the cell surface. The supernatant was discarded, and pure DMEM was added to a final volume of 10 mL to resuspend the cells. Cells were counted using a cell counter (the specific counting method varies depending on the cell counter). The cells were centrifuged at 1000 rpm for 5 min, the supernatant was discarded, and pure DMEM was added to resuspend the cells to a final concentration of 1×10⁻⁶. 9 The injection volume per C57BL / C male mouse is calculated as 5 μL, with a volume of 1000 ions / mL.

[0026] C57BL / C male mice were anesthetized by intraperitoneal injection of 0.9% sodium pentobarbital at a dose of 10 uL / g. The scalp of the C57BL / C male mice was longitudinally incised with scissors, and 3% hydrogen peroxide solution was applied to the skull surface to expose the anterior fontanelle. A 1 mL syringe needle was used to make an incision 2 cm to the right and 1 cm above the anterior fontanelle (located in the basal ganglia region). The C57BL / C male mice were fixed in a stereotactic injection apparatus. Prepared cells were aspirated and slowly injected through the incision, with 5 uL of cells injected into each C57BL / C male mouse. The entire process lasted approximately 5 minutes. Min, be careful not to inject too quickly, otherwise it may cause cell extravasation; remove the injected C57BL / C male rat from the stereotaxic instrument and seal the opening with bone wax; suture the scalp of the C57BL / C male rat with 3-0 sutures; gently place the sutured C57BL / C male rat on a 37℃ heating blanket, and after the C57BL / C male rat wakes up, put it back into the corresponding cage according to the group and mark it; observe the survival and movement of the C57BL / C male rat on the second day.

[0027] 2. Irradiation therapy of glioma in situ animal model: Two weeks after modeling, C57BL / C male mice in each group were irradiated according to experimental requirements.

[0028] 3. Supplementation of arginine and proline in drinking water: Starting from the second day after modeling, arginine and proline powders were dissolved in the mice's drinking water to prepare a drinking water concentration of 40 g / L. The drinking water was changed every three days until the mice were sacrificed.

[0029] 4. MRI examination of tumor formation in C57BL / C male mice: Two weeks later, C57BL / C male rats were anesthetized by intraperitoneal injection of 0.9% sodium pentobarbital at a dose of 10 μL / g. After the C57BL / C male rats were completely paralyzed, gadolinium was injected intraperitoneally at a dose of 5 μL / g. MRI images of C57BL / C male rats were taken, and the intracranial tumor volume of C57BL / C male rats was estimated according to the formula. The differences in tumor volume between the control group, the arginine group and the proline group of C57BL / C male rats were analyzed and compared.

[0030] 5. Determination of arginine concentration in mouse serum: After removing the mouse serum sample from the -80℃ freezer, thaw it at 4℃. Take out the arginine enzyme-linked immunosorbent assay kit (Cat# ml012897B, ELISA) 1 hour in advance and bring it to room temperature. Take the concentrated washing buffer (20X) and dilute it with double-distilled water at a ratio of 1:19.

[0031] Set up the plate with standard wells, blank wells, and sample wells. Add 50 μL of standard at different concentrations to each standard well, leave the blank wells empty, and add 50 μL of the sample to be tested to each sample well. The standard concentrations are: 300, 150, 75, 37.5, 18.75, and 0 mmol / L, respectively. Add HRP enzyme conjugation working solution: except for the blank wells, add 100 μL of horseradish peroxidase (HRP) labeled detection antigen to the standard wells and sample wells.

[0032] Incubation: Cover the reaction plate with a sealing film and incubate at 37 ℃ in a water bath or incubator for 60 min.

[0033] Washing the plate: Remove the sealing film, discard the liquid, pat dry on absorbent paper, fill each well with washing solution, let stand for 20 seconds, shake off the washing solution, pat dry on absorbent paper, and repeat this process 5 times.

[0034] Color development: Mix substrates A and B thoroughly at a 1:1 volume ratio, and add 100 μL of the substrate mixture to all wells. Cover the reaction plate with sealing film and incubate at 37°C in a water bath or incubator for 15 min. Substrate A and B should be used within 15 min after mixing.

[0035] Termination: Add 50 μL of stop solution to all wells and read the absorbance (OD value) of each well on a microplate reader.

[0036] Measurement: Immediately measure the OD value of each well at 450 nm and 37°C using an ELISA reader.

[0037] Analysis: Calculate the average OD values ​​of the standard and replicates, plot the concentration on the x-axis and the OD value on the y-axis in Excel, and fit the corresponding scatter plot to obtain a standard curve. Substitute the OD values ​​measured in the sample wells into the function of the standard curve to obtain the serum arginine concentration (mmol / L) corresponding to the patient sample.

[0038] 5. Determination of proline concentration in mouse serum: After removing the serum sample from the -80 ℃ freezer, thaw it at 4 ℃. Take the proline micro-assay kit (PRO-W96-N (1620), ELISA) out beforehand and allow it to equilibrate to room temperature. Preheat the ELISA reader for at least 30 min, adjust the wavelength to 520 nm, and zero the instrument with distilled water.

[0039] Sample preparation: Take 50 μL of serum sample and add 500 μL of extraction buffer at a ratio of serum volume (mL): extraction buffer volume (mL) of 1:5~10 (it is recommended to take 0.1 mL of serum and add 1 mL of extraction buffer). Mix thoroughly, then place in a 95℃ water bath and shake for 10 minutes. Centrifuge at 10000 g and 25℃ for 10 minutes. Take the supernatant, cool it and wait for testing.

[0040] Sample determination: (1) Take 0.25 mL of sample + 0.25 mL of reagent one (prepare glacial acetic acid) + 0.25 mL of reagent two into a capped EP tube, place it in a 95℃ water bath for 30 min (tightly capped to prevent moisture loss), and shake once every 10 min.

[0041] (2) After cooling, add 0.5 mL of reagent three (prepared toluene or xylene), shake for 30 s, let stand for a while, and let the pigment transfer to reagent three; take 0.2 mL of the upper layer solution into a 96-well plate, measure the absorbance at a wavelength of 520 nm, and record the absorbance OD value (A below).

[0042] Analysis: The calculation formula for the 96-well plate test is as follows: (1) The typical regression equation is y = 0.02605x - 0.0021 Where x represents the proline content (μg / mL) and y represents the absorbance value A; (2) Calculated based on serum (plasma) volume Pro content (μg / mL) = [(A + 0.0021) ÷ 0.02605 × V1] ÷ (V3 × V1 ÷ V2) =384×(A+0.0021) II. Clinical For glioma patients (standard: selected postoperative patients, blood samples before the first irradiation and blood samples after the end of the treatment course were used for arginine and proline testing combined with efficacy evaluation), several milliliters of venous blood were collected from the patient in the morning on an empty stomach before irradiation and after the start of the irradiation treatment course. The blood was placed in 5 mL EP tubes and allowed to stand at room temperature for 1 hour to allow the blood to clot and separate into layers. The blood was centrifuged at 3000 rpm for 20 minutes at room temperature. The centrifuged blood sample was carefully removed from the centrifuge and placed on a test tube rack. The blood sample was visibly divided into two distinct layers: the upper layer was pale yellow, which was the required serum, and the lower layer was blood cell components. The upper serum layer was evenly divided into two EP tubes using a pipette and stored at -80°C.

[0043] Arginine and proline levels in patient serum were measured, referring to the detection method for arginine and proline in mouse serum.

[0044] like Figure 1 As shown in Figure A, the differences in arginine and proline concentrations in serum samples of glioma patients (n=12) before and after irradiation are evident. It is clear that in the serum of glioma patients, compared to before irradiation, arginine showed significantly higher specific expression after irradiation, while proline showed significantly lower specific expression, indicating poor irradiation efficacy. This embodiment also proposes to improve irradiation efficacy through interventions targeting arginine and proline levels.

[0045] like Figure 6 As shown in Figure A, the serum samples of mice with an in situ glioma tumorigenesis model showed differences in arginine and proline concentrations. It was observed that, compared to normal mice before and after irradiation and the group receiving arginine-added water, arginine was highly expressed in the irradiated control group, and the arginine content in the irradiated water-added arginine group was still higher than that in the irradiated control group. Conversely, compared to normal mice before and after irradiation and the group receiving proline in water, proline was lowly expressed in the irradiated control group, and the proline content in the irradiated water-added proline group was still higher than that in the irradiated control group.

[0046] like Figure 4 , 5 As shown, in mice with an in situ glioma tumor model, the in situ glioma tumors before irradiation grew significantly after in vivo administration of arginine supplementation compared to the untreated group; however, after irradiation stimulation, the volume of the in situ glioma tumors did not decrease significantly compared to the untreated group. In mice with an in situ glioma tumorigenesis model, the growth of glioma in situ tumors was significantly inhibited before irradiation compared to the untreated group after proline supplementation; and the volume of glioma in situ tumors was significantly reduced after irradiation compared to the untreated group.

[0047] It is evident that arginine supplementation can significantly increase tumor volume and enhance the efficacy of radiation therapy, while proline supplementation can significantly reduce tumor volume and enhance the efficacy of radiation therapy.

[0048] Example 2 I. Animal Experiments: 1. Construction of an orthotopic animal model of breast cancer: The murine breast cancer cell line 4T1 was cultured in TC-treated T225 flasks to 80%-90% confluence. The culture medium was discarded, and the cells were washed once with PBS. A suitable amount of trypsin was added to digest pancreatic cancer cells into single cells. A suitable amount of complete culture medium was added to neutralize the trypsin, and the cells were transferred to 15 mL centrifuge tubes. Microscopic examination confirmed that no cells remained at the bottom of the flask. The cells were centrifuged at 1000 rpm for 5 min. The supernatant was discarded, and the cells were resuspended in 10 mL of pure DMEM. The cells were centrifuged at 1000 rpm for 5 min. This step was repeated four times to remove residual FBS on the cell surface. The supernatant was discarded, and pure DMEM was added to a final volume of 10 mL to resuspend the cells. Cells were counted using a cell counting chamber. The cells were centrifuged at 1000 rpm for 5 min, the supernatant was discarded, and pure DMEM was added to resuspend the cells to a final concentration of 5 × 10⁻⁶ cells / mL. 6 The injection volume per 100 mice was calculated as 200 μL, with each female BalbL / C mouse injected at a rate of 100 μL / mL.

[0049] Inject 200 μL of cell suspension into the fat pad of the fourth pair of nipples on the left side of the mouse using a 1 mL syringe, diagonally through the fifth pair of nipples. After successful injection, a slightly bulging wheal will form at the nipple site. Keep the syringe in place and carefully remove it after 20 seconds. Observe the general condition of the Balb / C female mice on the second day after surgery and observe the tumor formation. Starting from the fifth day, measure the tumor size every two days.

[0050] 2. Irradiation therapy in an orthotopic animal model of breast cancer: Two weeks after modeling, the female Balb / C mice in each group underwent irradiation treatment as required by the experiment.

[0051] 3. Supplementation of arginine and proline in drinking water: Starting from the second day after modeling, arginine and proline powders were dissolved in the mice's drinking water to prepare a drinking water concentration of 40 g / L. The drinking water was changed every three days until the mice were sacrificed.

[0052] 4. Obtaining mouse tumor tissue to detect breast cancer tumor formation: Balb / C female mice were anesthetized with isoflurane, and their hearts were perfused once with physiological saline and then once with paraformaldehyde. The tumor tissue of the corresponding mice was then removed and the differences in tumor volume between the control group, arginine group and proline group of Balb / C female mice were analyzed and compared.

[0053] 5. Determination of arginine concentration in mouse serum: After removing the mouse serum sample from the -80℃ freezer, thaw it at 4℃. One hour in advance, take out the arginine enzyme-linked immunosorbent assay kit (Cat# ml012897B, ELISA) and bring it to room temperature. Take the concentrated washing buffer (20X) and dilute it with double-distilled water at a ratio of 1:19.

[0054] Set up the plate with standard wells, blank wells, and sample wells. Add 50 μL of standard at different concentrations to each standard well, leave the blank wells empty, and add 50 μL of the sample to be tested to each sample well. The standard concentrations are: 300, 150, 75, 37.5, 18.75, and 0 mmol / L, respectively. Add HRP enzyme conjugation working solution: except for the blank wells, add 100 μL of horseradish peroxidase (HRP) labeled detection antigen to the standard wells and sample wells.

[0055] Incubation: Cover the reaction plate with a sealing film and incubate at 37°C in a water bath or incubator for 60 min.

[0056] Washing the plate: Remove the sealing film, discard the liquid, pat dry on absorbent paper, fill each well with washing solution, let stand for 20 seconds, shake off the washing solution, pat dry on absorbent paper, and repeat this process 5 times.

[0057] Color development: Mix substrates A and B thoroughly at a 1:1 volume ratio, and add 100 μL of the substrate mixture to all wells. Cover the reaction plate with sealing film and incubate at 37°C in a water bath or incubator for 15 min. Substrate A and B should be used within 15 min after mixing.

[0058] Termination: Add 50 μL of stop solution to all wells and read the absorbance (OD value) of each well on a microplate reader.

[0059] Measurement: Immediately measure the OD value of each well at 450 nm and 37°C using an ELISA reader.

[0060] Analysis: Calculate the average OD values ​​of the standard and replicates, plot the concentration on the x-axis and the OD value on the y-axis in Excel, and fit the corresponding scatter plot to obtain a standard curve. Substitute the OD values ​​measured in the sample wells into the function of the standard curve to obtain the serum arginine concentration (mmol / L) corresponding to the patient sample.

[0061] 6. Determination of proline concentration in mouse serum: After removing the serum sample from the -80℃ freezer, thaw it at 4℃. Beforehand, remove the proline microassay kit (PRO-W96-N (1620), ELISA) and allow it to equilibrate to room temperature. Preheat the ELISA reader for at least 30 minutes, adjust the wavelength to 520nm, and zero the instrument with distilled water.

[0062] Sample preparation: Take 50 μL of serum sample and add 500 μL of extraction buffer at a ratio of serum volume (mL): extraction buffer volume (mL) of 1:5~10 (it is recommended to take 0.1 mL of serum and add 1 mL of extraction buffer). Mix thoroughly, then place in a 95℃ water bath and shake for 10 minutes. Centrifuge at 10000 g and 25℃ for 10 minutes. Take the supernatant, cool it and wait for testing.

[0063] Sample determination: (1) Take 0.25 mL of sample + 0.25 mL of reagent one (prepare glacial acetic acid) + 0.25 mL of reagent two into a capped EP tube, place it in a 95℃ water bath for 30 min (tightly capped to prevent moisture loss), and shake once every 10 min.

[0064] (2) After cooling, add 0.5 mL of reagent three (prepared toluene or xylene), shake for 30 s, let stand for a while, and let the pigment transfer to reagent three; take 0.2 mL of the upper layer solution into a 96-well plate, measure the absorbance at a wavelength of 520 nm, and record the absorbance OD value (A below).

[0065] Analysis: The calculation formula for the 96-well plate test is as follows: (1) The typical regression equation is y = 0.02605x - 0.0021 Where x represents the proline content (μg / mL) and y represents the absorbance value A; (2) Calculated based on serum (plasma) volume Pro content (μg / mL) = [(A + 0.0021) ÷ 0.02605 × V1] ÷ (V3 × V1 ÷ V2) =384×(A+0.0021) II. Clinical Breast cancer patients (standard: selected post-operative patients, blood samples before the first irradiation and blood samples after the end of the treatment course were used for arginine and proline testing combined with efficacy evaluation) had several milliliters of venous blood collected in the morning before irradiation and after the start of the irradiation treatment course, on an empty stomach. The blood was placed in 5 mL EP tubes and allowed to stand at room temperature for 1 hour to allow the blood to clot and separate into layers. The blood was centrifuged at 3000 rpm for 20 min at room temperature. The centrifuged blood sample was carefully removed from the centrifuge and placed on a test tube rack. The blood sample was visibly divided into two distinct layers: the upper layer was pale yellow, which was the required serum, and the lower layer was blood cell components. The upper serum layer was evenly divided into two EP tubes using a pipette and stored at -80°C.

[0066] Arginine and proline levels in patient serum were measured, referring to the detection method for arginine and proline in mouse serum.

[0067] like Figure 1 As shown in Figure B, the differences in arginine and proline concentrations in serum samples from breast cancer patients (n=12) before and after irradiation are evident. It is observed that in the serum of glioma patients, compared to before irradiation, arginine showed significantly higher specific expression after irradiation, while proline showed significantly lower specific expression, indicating poor irradiation efficacy. This embodiment also proposes to improve irradiation efficacy through interventions targeting arginine and proline levels. Figure 6 As shown in Figure B, the serum concentrations of arginine and proline in mice with an in situ breast cancer tumor model differ. It is evident that, compared to normal mice before and after irradiation and the group receiving arginine-added water, arginine expression was high in the irradiated control group, and the arginine content in the irradiated water-added arginine group was still higher than that in the irradiated control group. Conversely, compared to normal mice before and after irradiation and the group receiving proline in water, proline expression was low in the irradiated control group, and the proline content in the irradiated water-added proline group was still higher than that in the irradiated control group.

[0068] like Figure 2 , 3 As shown, in mice with an in situ breast cancer tumor model, the growth of in situ breast tumors before irradiation was more significant than that in the untreated group after in vivo administration of arginine supplementation; however, the volume of in situ breast tumors did not decrease significantly compared to the untreated group after irradiation stimulation. In mice with an in situ tumorigenesis model of breast tumors, the growth of in situ breast tumors before irradiation was significantly inhibited compared with the untreated group after in vivo administration of proline supplementation; after irradiation stimulation, the volume of in situ breast tumors was significantly reduced compared with the untreated group.

[0069] It is evident that arginine supplementation can significantly increase tumor volume and enhance the efficacy of radiation therapy, while proline supplementation can significantly reduce tumor volume and enhance the efficacy of radiation therapy.

[0070] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. The application of a biomarker for enhancing the radiotherapy efficacy of solid tumors in the preparation of products for improving the radiosensitivity of solid tumors, characterized in that, The biomarkers for enhancing the efficacy of radiotherapy for solid tumors are arginine and / or proline.

2. The application according to claim 1, characterized in that, The solid tumors include breast cancer and glioma.

3. A product for improving the radiosensitivity of solid tumors, characterized in that, The products include arginine inhibitors and / or proline supplements.

4. The product according to claim 3, characterized in that, The arginine inhibitor and / or proline supplement are preparations used to reduce tumor volume.

5. The product according to claim 3, characterized in that, The products mentioned are reagents and reagent kits.

6. The application of a biomarker for predicting the prognosis of solid tumors in the preparation of a detection product for predicting the prognosis and treatment efficacy of solid tumors, characterized in that, The biomarkers for predicting the prognosis of solid tumors are arginine and / or proline.

7. The application according to claim 6, characterized in that, The prognostic measure is radiotherapy.

8. The application according to claim 6, characterized in that, The solid tumors include breast cancer and glioma.

9. The application according to claim 6, characterized in that, The detection products are reagents, kits, test strips, or chips.

10. A diagnostic product for predicting the prognosis and treatment efficacy of solid tumors, characterized in that, This includes reagents for detecting arginine and / or proline content.

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