KR20240150715A - miR-6880-5p in cancer cell derived exosomes as biomarker for prostate cancer diagnosis - Google Patents

Abstract

The present invention relates to the use of miR-6880-5p in exosomes derived from cancer cells for prostate cancer diagnosis. The present invention is a diagnostic method using blood, which reduces the risk of tissue biopsy and overcomes the low accuracy rate in the PSA gray zone of the conventional technology to diagnose prostate cancer more accurately and quickly. In addition, it can be used to predict the prognosis for the treatment response to endocrine therapy.

Description

miR-6880-5p in cancer cell derived exosomes as biomarker for prostate cancer diagnosis

The present invention relates to the use of miR-6880-5p in exosomes derived from cancer cells for the diagnosis of prostate cancer, and more particularly, to a pharmaceutical composition for the diagnosis of prostate cancer, which provides the expression level of miR-6880-5p in exosomes in a plasma sample as a biomarker for the diagnosis of prostate cancer, and includes an agent capable of detecting miR-6880-5p as an active ingredient.

Prostate cancer (PCa) is the second most common malignant tumor among male cancers worldwide. According to the 2019 National Cancer Registry Statistics, the cancer incidence rate increased by 3.6% compared to the previous year, and prostate cancer was reported to be the 6th most common cancer (16,803 cases) when divided by cancer type. The incidence rates of stomach cancer, colon cancer, and liver cancer, which are more common than prostate cancer, have been decreasing for the past 10 years, but prostate cancer has been reported to have been continuously increasing since 1999.

Prostate cancer has various intratumor heterogeneities. Tumor heterogeneity is observed differently depending on the location of the information on the genotype and phenotype of cells within the tumor, and depending on the degree, it can affect drug response, treatment resistance, etc. Therefore, it is very important to understand the formation and progression pattern of the tumor through the degree of tumor heterogeneity in selecting a treatment method for the patient. Currently, prostate cancer is diagnosed and predicted through PSA (Prostate Specific Antigen) measurement, ultrasound examination, CT examination, MRI examination, and pathological tissue examination using tissue samples.

PSA is an enzyme secreted from prostate cells that is secreted into semen and a small amount of the enzyme is secreted into the blood. Therefore, the test is performed through the blood PSA level, and most normal people show a level of less than 4ng/ml. If this level is abnormally elevated, it is considered that there are diseases such as benign prostatic hyperplasia, prostatitis, and prostate cancer. However, since the accuracy of prostate cancer diagnosis in the PSA gray zone is about 30%, overdiagnosis and overtreatment may occur. Therefore, a tissue examination is required for an accurate diagnosis, and an appropriate treatment method is selected by considering the clinical stage, malignancy of cancer cells, and other diseases through a pathological tissue examination. However, a tissue examination is not only difficult to perform depending on the location, size, and condition of the tumor, but also invasive to the human body, so it is risky for patients and doctors, so a technology that can diagnose more simply and accurately is needed.

Haneul Lee et al., “Isolation and Characterization of Urinary Extracellular Vesicles from Healthy Donors and Patients with Castration-Resistant Prostate Cancer”, Int. J. Mol. Sci. 2022, 23, 7134

The present invention provides a method for diagnosing and predicting the prognosis of prostate cancer containing miR-6880-5p in exosomes. As a diagnostic method using blood, it reduces the risk of tissue biopsy and overcomes the low accuracy rate in the PSA gray zone of the conventional technology to diagnose prostate cancer more accurately and quickly. In addition, the purpose of the present invention is to provide a biomarker that can predict the prognosis for the treatment response to endocrine therapy. In addition, the present invention aims to provide a kit for predicting prostate cancer metastasis or prognosis containing the composition.

However, the technical problems to be achieved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

The present invention provides miR-6880-5p in exosomes separated from plasma as a biomarker for diagnosing prostate cancer and predicting the prognosis for treatment response.

In addition, the present invention provides a biomarker composition for diagnosing prognosis and predicting treatment response of prostate cancer, comprising miR-6880-5p in exosomes separated from plasma as an active ingredient.

As one embodiment of the present invention, the exosome may be a cancer-derived exosome, and the cancer-derived exosome may be isolated using a CD63 specific antibody.

In addition, the present invention provides a composition for diagnosing prostate cancer and predicting the prognosis for treatment response, comprising as an active ingredient an agent capable of measuring the expression level of miR-6880-5p in exosomes separated from plasma.

As one embodiment of the present invention, the agent capable of measuring the expression level of the miR-6880-5p may be an oligonucleotide comprising a nucleotide sequence complementary to part or all of the miR-6880-5p, and a non-limiting example thereof may be a primer or probe specific for the miR-6880-5p.

In addition, the present invention provides a method for diagnosing prostate cancer and a method for providing information for diagnosing prostate cancer, including the steps of isolating exosomes from a liquid biopsy isolated from a subject requiring diagnosis of prostate cancer; measuring the expression level of miR-6880-5p in the exosomes; and determining that the subject has prostate cancer if the expression level of miR-6880-5p is lower than that of a normal subject.

In addition, the present invention provides a method for determining the suitability of a treatment method in a prostate cancer patient by performing the following steps before and after the cancer treatment step: a step of isolating exosomes from a liquid biopsy isolated from the patient; a step of measuring the expression level of miR-6880-5p in the exosomes; and a step of determining that the treatment prognosis is likely to be good if the expression level of miR-6880-5p after the treatment is significantly higher than the expression level of miR-6880-5p before the treatment, and a step of determining that the treatment prognosis is likely to be poor if the expression level of miR-6880-5p is significantly lower than the expression level of miR-6880-5p before the treatment.

The present invention can be used as a diagnostic biomarker for predicting the onset of prostate cancer and the response to treatment by utilizing the specific expression pattern of blood-derived exosomal miRNA in prostate cancer patients. By analyzing using blood, a simpler and faster diagnosis can be made in a non-invasive manner. Exosomes in the blood have a phospholipid bilayer structure, and thus the expression pattern of miRNA can be confirmed using qPCR in a more stable manner.

Figure 1 shows the results of analyzing the characteristics of cancer cell-derived exosomes isolated from the blood of prostate cancer patients.
Figure 2 shows differentially expressed genes in exosomes derived from the blood of prostate cancer patients and normal people.
Figure 3 is a graph comparing the expression levels of miR-6880-5p in exosomes derived from the blood of prostate cancer patients and normal people.
Figure 4 is a graph showing the change in the expression level of miR-6880-5p before and after endocrine therapy in the PR group with a good treatment response and the PD group with a poor treatment response.
Figure 5 compares the expression levels of miR-6880-5p in various types of prostate cancer cells.

The present inventors have conducted a preliminary study on a method for diagnosing prostate cancer by a noninvasive method, identified low levels of miR-6880-5p in exosomes isolated from the blood of prostate cancer patients, and provided miR-6880-5p as a biomarker for diagnosing prostate cancer.

Meanwhile, the inventors of the present invention confirmed the change in the expression level of miR-6880-5p before and after endocrine therapy in groups with a good and poor prognosis for endocrine therapy. As a result, in the group with a good prognosis, a low level of miR-6880-5p was found to increase after treatment, and in the group with a poor prognosis, a relatively high level of miR-6880-5p was found and its expression level decreased after treatment.

Accordingly, the present inventors provide miR-6880-5p as a biomarker for predicting treatment response in prostate cancer patients.

The present invention is characterized by using microRNA biomarkers as noninvasive tools for diagnosing prostate cancer and predicting therapeutic response to endocrine therapy in prostate cancer patients.

More specifically, the present invention provides a technology for determining that a patient in a sample has prostate cancer by measuring the expression level of miRNA-6880-5p present in the sample and determining that the patient in the sample has prostate cancer when miRNA-6880-5p is relatively underexpressed.

In the present invention, the transcript base sequence of miRNA-6880-5p is 5'-UGGUGGAGGAAGAGGGCAGCUC-3' (SEQ ID NO: 1) (Accession Number: MIMAT0027660).

In the present invention, the case where miRNA-6880-5p is relatively underexpressed is based on the expression level of miRNA-6880-5p in exosomes isolated from the plasma of a normal person. In order to determine that the patient in question has prostate cancer, the expression level should be about 0.8 times or less than the expression level of miRNA-6880-5p in a normal person, and preferably, an underexpression of about 0.6 times or less should be confirmed.

Various agents capable of detecting microRNA can be used to measure the expression level of miRNA-6880-5p present in a sample.

In the present invention, “diagnosis” includes determining the susceptibility of an individual to a specific disease or condition, determining whether an individual currently has a specific disease or condition, determining the prognosis of an individual with a specific disease or condition, or therametrics (e.g., monitoring the condition of an individual to provide information about the efficacy of a treatment).

In addition, the prostate cancer diagnostic kit of the present invention may include an agent capable of measuring the expression level of miRNA-6880-5p from a biological sample, wherein the agent means a molecule that can be used for detecting the biomarker of the present invention by confirming the expression level of miRNA-6880-5p.

In the present invention, an antisense oligonucleotide, primer, probe, and/or antibody that specifically binds to miRNA-6880-5p can be used as a miRNA-6880-5p expression level measuring agent, and the expression level of miRNA-6880-5p can be measured by a known method used to measure the level of gene expression, for example, performing PCR using a primer, or performing a hybridization reaction using a probe. In addition, in addition to the measuring agent, the kit may include various tools and reagents known in the art that facilitate detection, for example, a suitable carrier, a labeling substance capable of generating a detectable signal, a stabilizer, etc.

The biological sample used to measure the expression level of miRNA-6880-5p in the present invention may be a non-invasive sample, and the non-invasive sample may be a liquid biopsy, i.e., blood, serum, plasma, urine, or saliva, preferably blood, serum, or plasma, and more preferably plasma, but is not limited thereto.

In the present invention, miRNA-6880-5p is a concept that includes functional equivalents of the oligonucleotides constituting it, for example, variants and mimics that can perform functionally the same function as the microRNA-6880-5p nucleic acid molecule, although some of the base sequences of the miRNA-6880-5p oligonucleotide have been modified by deletion, substitution, or insertion.

In the present invention, the “primer” refers to a short nucleic acid sequence having a short free hydroxyl group, which can form base pairs with a complementary template and serves as a starting point for copying the template strand. The primer of the present invention can be chemically synthesized using a method known in the art, such as, for example, a phosphoramidite solid support method.

In the present invention, the “probe” refers to a nucleic acid fragment such as RNA or DNA consisting of several to several hundred bases that can specifically bind to miRNA and is labeled so that the presence or absence of a specific miRNA can be confirmed. The probe can be produced in the form of an oligonucleotide probe, a single-stranded DNA probe, a double-stranded DNA probe, an RNA probe, etc., and can be labeled with biotin, FITC, rhodamine, DIG, etc., or labeled with a radioisotope, etc.

In the present invention, the kit may be a kit including essential elements necessary for performing RT-PCR, but is not limited thereto. As an example, in the case of an RT-PCR kit, in addition to each primer pair specific for a marker gene, the kit may include a test tube or other appropriate container, a reaction buffer, deoxynucleotides (dNTPs), Taq polymerase and reverse transcriptase, DNase, RNase inhibitor, DEPC-water, sterile water, and the like.

In addition, the present invention can provide a method for diagnosing prostate cancer and a method for providing information for diagnosing prostate cancer, including the steps of isolating exosomes from a liquid biopsy isolated from a subject requiring diagnosis of prostate cancer; measuring the expression level of miR-6880-5p in the exosomes; and determining that the subject has prostate cancer if the expression level of miR-6880-5p is lower than that of a normal subject.

The measurement of the above miRNA expression level can be performed by, but is not limited to, RT-PCR, competitive RT-PCR, real-time RT-PCR, quantitative RT-PCR, RNase protection assay (RPA), Northern blotting, or DNA chip method.

In the present invention, prevention means all acts of delaying the occurrence of prostate cancer by administering the composition according to the present invention, treatment means suppressing the survival and proliferation of prostate cancer by administering the pharmaceutical composition according to the present invention, and “metastasis” in the present invention means that prostate cancer moves away from the site of occurrence, and prevention or suppression of metastasis means all acts of reducing the movement and invasiveness of prostate cancer cells to reduce the departure of cancer cells from the site of occurrence.

In addition, the subject to be administered the pharmaceutical composition of the present invention is not limited to a mammal, but may preferably be a human, and more specifically, may be a prostate cancer patient.

The pharmaceutical composition of the present invention may further include suitable carriers, excipients, and diluents commonly used in the manufacture of pharmaceutical compositions.

In the present invention, the term "carrier", also called a vehicle, means a compound that facilitates the addition of a protein or peptide into a cell or tissue. For example, dimethyl sulfoxide (DMSO) is a commonly used carrier that facilitates the introduction of many organic substances into the cells or tissues of a living organism.

In the present invention, a "diluent" is defined as a compound that is diluted in water, which not only stabilizes the biologically active form of the target protein or peptide, but also dissolves the protein or peptide. A salt dissolved in a buffer solution is used as a diluent in the art. A commonly used buffer solution is phosphate buffered saline, because it mimics the salt state of human solutions. Since the buffer salt can control the pH of the solution at low concentrations, it is rare for a buffer diluent to modify the biological activity of the compound. The compounds containing azelaic acid used herein can be administered to a human patient as such, or as a pharmaceutical composition mixed with other ingredients or with suitable carriers or excipients, as in combination therapy.

In addition, the pharmaceutical composition for preventing or treating non-alcoholic steatohepatitis according to the present invention can be formulated and used in the form of external preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. and sterile injection solutions according to conventional methods, and carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants that are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and these solid preparations are prepared by mixing the compound with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin butter, and glycerogelatin.

The pharmaceutical composition of the present invention can be administered orally or parenterally, preferably parenterally, and in the case of parenteral administration, can be administered by intramuscular injection, intravenous injection, subcutaneous injection, intraperitoneal injection, topical administration, transdermal administration, etc.

The appropriate dosage of the pharmaceutical composition of the present invention can be prescribed in various ways depending on factors such as the formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity.

The pharmaceutical composition of the present invention can be manufactured in the form of a unit dose or can be manufactured by placing it in a large-capacity container by formulating it using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by a person having ordinary skill in the art to which the present invention pertains, and by being formulated. At this time, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granules, tablets or capsules, and may additionally contain a dispersant or stabilizer.

The present invention can be modified in various ways and has various embodiments, and thus specific embodiments are illustrated in the drawings and described in detail in the detailed description below. However, this is not intended to limit the present invention to specific embodiments, and it should be understood that all modifications, equivalents, and substitutes included in the spirit and technical scope of the present invention are included. In describing the present invention, if it is determined that a specific description of a related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.

[Example]

Example 1. Plasma separation

Blood from normal subjects and prostate cancer patients was centrifuged at 2500 rpm for 7 minutes to separate plasma. The separated plasma was dispensed into cryovial tubes (550 ㎕ each) and stored at -80℃ until use in the experiment.

Example 2. Exosome isolation

The separated plasma samples were preprocessed in three steps.

1) After centrifugation at 1,200 g, 20 minutes, and 4℃, the supernatant was collected.

2) The supernatant was centrifuged once more at 10,000 g, 30 minutes, and 4°C, and then the supernatant was collected.

3) Finally, the separated supernatant was filtered using a 0.2 ㎛ syringe to remove large molecules.

The preprocessed samples were reacted with immuno-magnetic beads conjugated with CD63 antibody, an exosome surface marker, using a roller for 2 hours, and exosomes were separated using elution buffer. The separated exosomes were stored at -80℃ until used in the experiment.

Example 3. Exosome identification

The size and concentration of the isolated exosomes were analyzed using NanoSight LM10. After diluting 1:10 in PBS, the exosomes were injected into the sample measurement chamber using a 1 ㎖ syringe while minimizing bubble formation. Data analysis was performed using NTA Version 2.3 Build 0034 software.

Through this experiment, the size, concentration, and shape of the separated exosomes were confirmed to confirm whether they were exosomes (Figure 1).

Example 4. Selection of miRNAs in exosomes for prostate cancer diagnosis

-80℃ stored plasma was thawed and exosomes were isolated using CD63 antibody-conjugated immunomagnetic beads. miRNA from exosomes was isolated using Invitrogen (Cat No. 4478545) according to the manufacturer's instructions. Total RNA extracted from exosomes was labeled with fluorescent dye using FlsachTag Biotin RNA Labeling Kit to synthesize cDNA, and double-stranded DNA was converted to single-strand for hybridization. Then, it was hybridized to GeneChip miRNA 4.0 microarray. All arrays were measured by Affymetrix Gene Chip Scanner 3000, and data were analyzed by Transcriptome Analysis ConsoleTM (TAC) software. Differentially expressed genes were identified in the normalized miRNA data set using the R programming language (Fig. 2).

Through this experiment, we were able to identify miRNAs in plasma-derived exosomes that are differentially expressed between normal individuals and prostate cancer. In this result, PR is an abbreviation for Partial Response and refers to patients who respond well to treatment. PD is an abbreviation for Progressive disease and refers to a case in which one or more new lesions develop despite treatment. However, in this result, the samples of prostate cancer patients used the blood of patients before endocrine therapy. The experimental results showed that miR-6880-5p showed a significantly low expression level in the PD group and a relatively high expression level in the normal and PR groups. Therefore, it can be seen that the expression of miR-6880-5p in exosomes can distinguish prostate cancer patients from normal individuals and is related to the response to endocrine therapy in prostate cancer patients (Fig. 4).

Example 5. Confirmation of miRNA expression level in exosomes: qRT-PCR (Quantitative real-time polymerase chain reaction)

Total RNA in exosomes was isolated, and cDNA was synthesized using the TaqMan MicroRNA Reverse Transcription Kit and a primer with the sequence of has-miR-6880-5p (assay ID 467246_mat; 5'-UGGUGGAGGAAGAGGGCAGCUC-3'). 7 ㎕ of the reverse transcription kit mixture (100 mM dNTPs, MultiScribe Reverse Transcriptase, 10X Reverse Transcription Buffer, RNase inhibitor, Nuclease-free water), 3 ㎕ of 5X RT primer, and 5 ㎕ of RNA were added per sample (Table 1). Then, PCR was performed under the conditions of 16℃ for 30 min, 42℃ for 30 min, 85℃ for 5 min, and 4℃ ∞. The kit and primers for cDNA synthesis were purchased from Applied Biosystems, and PCR was performed according to the manufacturer's instructions. 1.33 ㎕ of synthesized cDNA, TaqMan master mix (2x), has-miR-6880-5p probe (TaqMan assay (20x)), and Ultra pure water were adjusted to a total of 20 ㎕ and dispensed into a 96-well standard (0.2 ㎖) plate (Table 2). qRT-PCR was performed for 1 cycle of 50℃ for 2 minutes, 1 cycle of 95℃ for 10 minutes, and 40 cycles of 95℃ for 15 seconds and 60℃ for 60 seconds to measure the expression of miR-6880-5p.

Through this experiment, the expression level of miR-68805p in blood-derived exosomes of prostate cancer patients was confirmed compared to that of normal people. By confirming that the expression of miR-6880-5p was decreased in prostate cancer patients compared to normal people, it was found that the expression of miR-6880-5p in exosomes is related to prostate cancer (Fig. 3a). In addition, the expression of miR-6880-5p before and after endocrine therapy in the PR and PD groups of prostate cancer was confirmed. In the PR group, the expression of miR-6880-5p increased after treatment (FU, follow-up) compared to before treatment (BL, baseline), and in the PD group, the expression of miR-6880-5p decreased after treatment compared to before treatment (Fig. 4).

Component Volume (1 reaction) 100mM dNTPs (with dTTP) 0.15 μL MutiScribe ^™ Reverse Transcriptase, 50 U/μL 1.00 μL 10 1.50 μL RNase Inhibitor, 20 U/μL 0.19 μL Nuclease-free Water 4.16 μL Total RT Reaction Mix volume 7.00 μL

Component Volume per reaction 384-well or 96-well fast [0.1 mL] plate 96-well standard [0.2mL] plate TaqMan ^TM Small RNA Assay [20X] 0.50 μL 1.00 μL PCR Master Mix 5.00 μL 10.00 μL Nuclease-free water 3.84 μL 7.67 μL Total PCR Reaction Mix volume 9.34 μL 18.67 μL

Example 6. Cell culture

In this study, the normal prostate epithelial cell line RWPE-1, the hormone-responsive prostate cancer cell line LNCaP, and the castration-resistant prostate cancer cell lines DU145 and PC3 were used. RWPE-1 was cultured in Keratinocyte Serum-Free Medium containing 0.05 mg/mL BPD, 0.005 μg/mL Epidermal Growth Factor, and 1% Penicillin-Streptomycin, and LNCaP, DU145, and PC3 cell lines were cultured in RPMA-1640 medium containing 10% FBS and 1% Penicillin-Streptomycin. All cells were cultured in an incubator at 5% CO2 and 37℃.

Example 7. Confirmation of miRNA expression level in prostate cancer cells

To confirm the expression of miR-6880-5p by prostate cancer type, miRNA was isolated from normal prostate epithelial cells and prostate cancer cells using QIAzol reagent, miRNeasy Mini kit (Qiagen, Cat No. 217004) according to the manufacturer's instructions. Then, cDNA was synthesized using the same method as the method for confirming the expression of miRNA obtained from exosomes, and the expression of miR-6880-5p in prostate cancer cells was confirmed through qRT-PCR.

As a result, it was found that the expression of miR-6880-5p was low in the order of RWPE-1, LNCaP, DU145, and PC3 (Fig. 5). Through the above results, it was found that it could be used to predict the prognosis of each type of prostate cancer according to the expression level of miR-6880-5p.

Although the embodiments have been described with limited drawings as described above, those skilled in the art can apply various technical modifications and variations based on the above. For example, even if the described techniques are performed in a different order than the described method, and/or the components of the described system, structure, device, circuit, etc. are combined or combined in a different form than the described method, or are replaced or substituted by other components or equivalents, appropriate results can be achieved.

Therefore, other implementations, other embodiments, and equivalents to the claims are also included in the scope of the claims described below.

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Claims (8)

A biomarker composition for diagnosing prostate cancer comprising miR-6880-5p in cancer cell-derived exosomes as an active ingredient. In the first paragraph,
The above cancer cell-derived exosomes were isolated from plasma.
A biomarker composition wherein the above cancer cell-derived exosomes express CD63. A composition for diagnosing prostate cancer, comprising as an active ingredient an agent capable of measuring the expression level of miR-6880-5p in cancer cell-derived exosomes. In the third paragraph,
A composition for diagnosing prostate cancer, wherein the agent capable of measuring the expression level of the above miR-6880-5p is an oligonucleotide containing a nucleotide sequence complementary to part or all of the above miR-6880-5p. (1) A step of isolating cancer cell-derived exosomes from a liquid biopsy isolated from an individual requiring diagnosis of prostate cancer;
(2) a step of measuring the expression level of miR-6880-5p in the exosome; and
(3) A method for diagnosing prostate cancer and a method for providing information for diagnosing prostate cancer, comprising: a step of determining that the patient has prostate cancer if the expression level of the miR-6880-5p is lower than that of a normal person. In paragraph 5,
An information providing method, wherein the step (1) above is performed using an immuno-magnetic bead combined with a CD63 antibody. In paragraph 5,
A method of providing information, wherein the liquid biopsy is blood, plasma, or serum. How to determine the appropriateness of treatment in patients with prostate cancer by performing the following steps before and after cancer treatment:
(a) isolating cancer cell-derived exosomes from a liquid biopsy isolated from the patient;
(b) a step of measuring the expression level of miR-6880-5p in the exosome; and
(c) a step of determining that the treatment prognosis is good if the expression level of the miR-6880-5p after treatment is significantly higher than that before treatment, and determining that the treatment prognosis is poor if the expression level is significantly lower than that before treatment.