CN113416784A - Serum exosome tsRNA marker related to breast cancer diagnosis and application thereof - Google Patents
Serum exosome tsRNA marker related to breast cancer diagnosis and application thereof Download PDFInfo
- Publication number
- CN113416784A CN113416784A CN202110810191.8A CN202110810191A CN113416784A CN 113416784 A CN113416784 A CN 113416784A CN 202110810191 A CN202110810191 A CN 202110810191A CN 113416784 A CN113416784 A CN 113416784A
- Authority
- CN
- China
- Prior art keywords
- breast cancer
- trf
- tsrna
- seq
- serum
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6851—Quantitative amplification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Abstract
The invention discloses a serum exosome tsRNA marker related to breast cancer diagnosis and application thereof, belonging to the fields of molecular biology and oncology. The markers are combinations of tRF-Glu-TTC-009, tRF-Gly-TCC-010, tRF-His-GTG-005 in serum exosomes tsRNA. The marker of the invention has higher sensitivity and specificity, and is helpful for auxiliary diagnosis of breast cancer.
Description
Technical Field
The invention belongs to the fields of molecular biology and oncology, and relates to a serum exosome tsRNA marker related to breast cancer and application thereof.
Background
The breast cancer is the tumor type with the highest morbidity and mortality of women, and according to statistics, the number of the breast cancer diseases is 210 ten thousand and the number of the breast cancer deaths is 63 ten thousand every year all over the world, and the breast cancer is the first malignant tumor of the women. At present, although the prognosis of breast cancer is better, the breast cancer is still the leading cause of death of women due to cancer because of higher morbidity.
At present, imaging examination, breast cancer marker detection and needle biopsy are the common clinical breast cancer diagnosis methods, but these methods have certain limitations: the PET-CT and other imaging methods can diagnose and detect the tiny tumor, but the equipment requirement is high, the operation is complicated, the actual treatment effect cannot be reflected from the molecular level, and the popularization and the application are limited; although some conventional breast cancer serum markers such as glycoprotein CA153, carcinoembryonic antigen CEA and the like can be used for breast cancer diagnosis, the sensitivity and the specificity are poor. The aspiration biopsy is the most reliable breast cancer diagnosis method at present, but has a certain false negative rate, can not accurately judge breast cancer, and is difficult to carry out early diagnosis and treatment effect monitoring on breast cancer. Therefore, screening sensitive and effective biomarkers, diagnosing and detecting the breast cancer at an early stage, and having great significance for improving the treatment and prognosis of the breast cancer.
tsRNAs (tRNA-derived small RNAs) are a novel class of small non-coding RNAs derived from tRNA maturates or precursors. Recent studies have found that tsRNA participates in the regulation of various physiological and pathological functions, such as tumors, nervous system diseases, stress, viral infection and the like.
In recent years, a great deal of research finds that non-coding small RNA stably existing in body fluid can be used as a molecular marker for disease diagnosis. Recent research shows that tsRNAs can exist stably in serum and are rich in the content, however, relevant research on tsRNAs in exosomes and breast cancer is not reported at present, so that screening of serum exosomes tsRNAs abnormally expressed in breast cancer as biomarkers and development of corresponding diagnostic kits are necessary for diagnosis and treatment of breast cancer.
Disclosure of Invention
The primary object of the present invention is to provide a serum exosome tsRNA marker, the abnormal expression of which is correlated with the development of breast cancer.
The second object of the invention is to provide primers and stem-loop primers for the above serum exosome tsRNA markers.
The third purpose of the invention is to provide the application of the serum exosome tsRNA marker and the primer thereof in the preparation of a breast cancer diagnosis kit.
The fourth object of the present invention is to provide a kit for breast cancer diagnosis.
In order to achieve the purpose, the invention adopts the following technical scheme:
a serum exosome tsRNA marker for breast cancer diagnosis, which is a combination of the following three sequences:
tRF-Glu-TTC-009：SEQ ID No.1；
tRF-Gly-TCC-010：SEQ ID No.2；
tRF-His-GTG-005：SEQ ID No.3。
the invention provides a stem-loop primer of the serum exosome tsRNA marker, which comprises the following components in part by weight:
the stem-loop primer of tRF-Glu-TTC-009 is SEQ ID No. 4;
the stem-loop primer of the tRF-Gly-TCC-010 is SEQ ID No. 5;
the stem-loop primer of the tRF-His-GTG-005 is SEQ ID No. 6.
The invention provides a primer of the serum exosome tsRNA marker, which comprises the following components in parts by weight:
the forward primer of tRF-Glu-TTC-009 is SEQ ID No. 7;
the forward primer of the tRF-Gly-TCC-010 is SEQ ID No. 8;
the forward primer of the tRF-His-GTG-005 is SEQ ID No. 9;
the reverse primer is a universal primer sequence, and the sequence of the reverse primer is shown as SEQ ID No. 10.
The invention provides an application of the serum exosome tsRNA marker, a primer of the tsRNA marker and a stem-loop primer of the tsRNA marker in preparation of a breast cancer diagnosis kit.
The invention provides a breast cancer diagnosis kit which is used for detecting the expression levels of tRF-Glu-TTC-009, tRF-Gly-TCC-010 and tRF-His-GTG-005 in serum exosomes.
In a further technical scheme, the breast cancer diagnostic kit comprises a serum Exosome separation reagent, wherein the reagent is Total Exosome Isolation (from serum) of life corporation (Invitrogen).
In a further technical scheme, the breast cancer diagnosis kit contains the primer of the tsRNA marker and/or the stem-loop primer of the tsRNA marker.
In a further technical scheme, the breast cancer diagnosis kit can also comprise reagents used in PCR reaction, including AMV reverse transcriptase, dNTP, buffer solution, MgCl2, Taq enzyme, DEPC water and the like.
Advantageous effects
The serum exosome tsRNAs provided by the invention as breast cancer diagnosis markers have the advantages that:
(1) the tsRNAs are novel molecular markers, are minimally invasive, have stable expression, are easy to detect, have higher sensitivity and specificity, and are beneficial to auxiliary diagnosis of breast cancer.
(2) The invention systematically researches the effect of the serum exosome tsRNAs in breast cancer diagnosis, obtains the serum exosome tsRNAs marker of the breast cancer, and discloses the clinical value of the serum exosome tsRNAs marker in the breast cancer diagnosis.
(3) The serum exosome tsRNAs kit is a comprehensive and systematic diagnostic kit, can be used for auxiliary early diagnosis of breast cancer patients, is helpful for reflecting the disease state of the patients, and provides better support for clinical treatment.
(4) The invention adopts a strict design and evaluation system, directly sequences the serum exosome tsRNAs by adopting a high-throughput sequencing technology at the initial stage, and performs multi-stage verification on a large sample by qRT-PCR, thereby ensuring the application of the serum exosome tsRNAs biomarkers and the diagnosis kit.
Drawings
FIG. 1 is a heat map analysis of tsRNA differentially expressed in serum exosomes from breast cancer patient groups versus healthy control groups.
FIG. 2 shows the expression levels of 3 tsRNAs in serum exosomes in breast cancer patients and healthy controls.
FIG. 3 is a ROC plot of the diagnostic effect of 3 tsRNAs on breast cancer patients and healthy controls.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings and examples.
Examples
A serum exosome tsRNA marker for breast cancer diagnosis, which is a combination of the following three sequences:
tRF-Glu-TTC-009：SEQ ID No.1；
tRF-Gly-TCC-010：SEQ ID No.2；
tRF-His-GTG-005：SEQ ID No.3。
the invention provides a stem-loop primer of the serum exosome tsRNA marker, which comprises the following components in part by weight:
the stem-loop primer of tRF-Glu-TTC-009 is SEQ ID No. 4;
the stem-loop primer of the tRF-Gly-TCC-010 is SEQ ID No. 5;
the stem-loop primer of the tRF-His-GTG-005 is SEQ ID No. 6.
The invention provides a primer of the serum exosome tsRNA marker, which comprises the following components in parts by weight:
the forward primer of tRF-Glu-TTC-009 is SEQ ID No. 7;
the forward primer of the tRF-Gly-TCC-010 is SEQ ID No. 8;
the forward primer of the tRF-His-GTG-005 is SEQ ID No. 9;
the reverse primer is a universal primer sequence, and the sequence of the reverse primer is shown as SEQ ID No. 10.
The invention provides an application of the serum exosome tsRNA marker, a primer of the tsRNA marker and a stem-loop primer of the tsRNA marker in preparation of a breast cancer diagnosis kit.
The invention provides a breast cancer diagnosis kit which is used for detecting the expression levels of tRF-Glu-TTC-009, tRF-Gly-TCC-010 and tRF-His-GTG-005 in serum exosomes.
The breast cancer diagnostic kit contains a serum Exosome separation reagent, and the reagent is Total Exosome Isolation (from serum) of life company (Invitrogen).
The breast cancer diagnosis kit contains the primer of the tsRNA marker and/or the stem-loop primer of the tsRNA marker.
The breast cancer diagnostic kit can also comprise reagents used in PCR reaction, including AMV reverse transcriptase, dNTP, buffer solution, MgCl2, Taq enzyme, DEPC water and the like.
According to the invention, a group of tsRNAs with high specificity and sensitivity related to breast cancer is searched by separating the serum exosome RNA of a breast cancer patient and a healthy female contrast matched with the breast cancer patient, and a breast cancer diagnosis kit for clinical detection is developed, so that help is provided for clinical diagnosis and screening of breast cancer. The method specifically comprises the following steps:
collecting clinical samples
The applicant collected 334 serum samples and 302 normal healthy control samples of breast cancer patients in the cancer hospital of Jiangsu province by Standard Operating Procedure (SOP) from 2017, and collected corresponding pathological data (including age, TMN stage, pathological type, WHO grade, etc.).
The collected patient samples met the following conditions: (1) imaging diagnosis, pathology confirmed new breast cancer cases; (2) the patient is not treated by operations, radiotherapy, chemotherapy and the like, and blood samples are collected before the operation; (3) healthy controls are women age-matched to the patient.
Small RNA high-throughput sequencing screening of differentially expressed tsRNA
(1) Selecting 30 breast cancer patients and 30 healthy control serum samples matched with the ages of the patients respectively, and separating serum exosomes by using Total Exosome Isolation (from serum) (Invitrogen) reagent;
(2) extracting exosome total RNA using trizol (invitrogen life technologies) method;
(3) high-throughput sequencing of small RNAs: firstly, performing PAGE electrophoresis recovery on the extracted exosome total RNA; linking the link primer enzyme on the 3 'end and the 5' end of the small RNA molecule: all sRNA library construction and deep sequencing were done by aksorics (shanghai, china). The sRNA library was constructed according to the agilent bioanalyzer 2100. The Illumina NextSeq instrument standard small RNA sequencing is carried out, and the sequencing type is 50bp single reading. Carrying out RT-PCR reaction and then sequencing on the machine; and fourthly, analyzing and processing the data.
(4) Breast cancer serum exosome differential tsRNA was compared according to sequencing analysis.
Multi-stage screening of qRT-PCR to verify differentially expressed tsRNA
(1) Serum samples (100 uL/sample) of 72 breast cancer patients and 72 age-matched healthy controls were isolated;
(2) extracting total RNA of exosome, and obtaining a cDNA sample through RNA reverse transcription reaction (stem-loop primer is used in the process);
(3) detecting the 10 tsRNAs with the most significant differential expression in the sequencing result in the sample by a qRT-PCR method (an upstream primer and a downstream primer are used in the process), and screening the tsRNAs with differential expression;
(4) further verifying the differential tsRNA expression screened in (3) in an additional 232 breast cancer patients and 200 healthy controls age-matched thereto;
(5) summary analysis to determine tsRNA differentially expressed in breast cancer;
(6) the clinical value of differential tsRNA for breast cancer diagnosis was analyzed.
Research and development of breast cancer serum exosome tsRNA diagnostic kit
(1) And in the early stage, copy difference and expression difference tsRNA between the breast cancer patient and a healthy control are analyzed through high-throughput sequencing, and serum exosome tsRNA with obvious difference in the breast cancer patient and the healthy control is screened and verified through a qRT-PCR technology to be used as an index for assisting breast cancer diagnosis. Finally, serum exosome tsRNA composition diagnostic markers tRF-Glu-TTC-009, tRF-Gly-TCC-010 and tRF-His-GTG-005, which are related to breast cancer, were screened in a total of 334 serum samples of breast cancer patients and 302 normal healthy control samples. A breast cancer diagnosis kit is developed on the basis, and comprises three stem-loop primers (used in the reverse transcription process) of tsRNA, upstream and downstream primers (used in qRT-PCR), an exosome separation reagent, AMV reverse transcriptase, Taq enzyme, MgCl2, DEPC water, dNTP and other reagents.
(2) Data analysis
All statistical tests were performed using GraphPad Prism software 8 (san diego, CA). Data are presented as mean ± SEMs. P < 0.05 is statistically significant for the differences.
The following is a further description of the invention:
in the preliminary screening stage, the present invention analyzes mixed serum exosomes of 30 breast cancer patients and 30 healthy controls by small RNA high-throughput sequencing, and 32 kinds of tsRNAs (cytoplasmic tsRNAs from GtRNAdb database; mitochondrial tsRNA predicted by tRNAscan-SE software) are found to be significantly increased (fold change > 2) in the serum exosome samples of the patients by screening, and the results are shown in FIG. 1.
According to the sequencing result, the first 10 tsRNAs with the most obvious increase in the serum exosomes of the breast cancer patients are selected for analysis, and the analysis comprises the following steps: tRF-Glu-TTC-009, tRF-Gln-TTG-009, tRF-Glu-TTC-010, tRF-Gly-GCC-034, tRF-Gly-TCC-010, tRF-His-GTG-005, tRF-Gly-TCC-016, tRF-Gly-CCC-043, tRF-Gln-TTG-012 and tRF-Val-CAC-008. Following one-to-one validation in 72 additional breast cancer patients and 72 healthy controls, 4 of the tsRNAs (tRF-Glu-TTC-009, tRF-Gly-TCC-010, tRF-His-GTG-005, and tRF-Gly-CCC-043) were significantly elevated in breast cancer patients. Subsequently, we continued to further analyze the expression of the above four tsRNAs in another 232 breast cancer patients and 200 healthy controls of serum exosomes. The results show that three tsRNAs, tRF-Glu-TTC-009, tRF-Gly-TCC-010 and tRF-His-GTG-005, were significantly increased in serum exosomes of breast cancer patients, and the results are shown in FIG. 2.
Then, the ROC Curve (Receiver Operating characterization Curve) further analyzes the diagnostic effect of the three tsRNAs on all breast cancer samples, and the result shows that the three tsRNAs have a better diagnostic effect on breast cancer, and have higher sensitivity (96.16%) and specificity (93.57%). The results are shown in FIG. 3.
Sequence listing
<110> Nanjing university of traditional Chinese medicine
<120> serum exosome tsRNA marker related to breast cancer and application thereof
<160> 10
<170> SIPOSequenceListing 1.0
<210> 1
<211> 28
<212> RNA
<213> Artificial Sequence (Artificial Sequence)
<400> 1
ucccacaugg ucuagcgguu aggauucc 28
<210> 2
<211> 32
<212> RNA
<213> Artificial Sequence (Artificial Sequence)
<400> 2
gcguuggugg uauaguggug agcauagcug cc 32
<210> 3
<211> 28
<212> RNA
<213> Artificial Sequence (Artificial Sequence)
<400> 3
gccgugaucg uauagugguu aguacucu 28
<210> 4
<211> 50
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 4
gtcgtatcca gtgcagggtc cgaggtattc gcactggata cgacggaatc 50
<210> 5
<211> 50
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 5
gtcgtatcca gtgcagggtc cgaggtattc gcactggata cgacggcagc 50
<210> 6
<211> 50
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 6
gtcgtatcca gtgcagggtc cgaggtattc gcactggata cgacagagta 50
<210> 7
<211> 21
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 7
cccacatggt ctagcggtta g 21
<210> 8
<211> 24
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 8
gttggtggta tagtggtgag cata 24
<210> 9
<211> 23
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 9
ggccgtgatc gtatagtggt tag 23
<210> 10
<211> 20
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<400> 10
Claims (10)
1. A serum exosome tsRNA marker associated with breast cancer diagnosis, characterized by: the marker is a combination of the following three sequences:
tRF-Glu-TTC-009：SEQ ID No.1；
tRF-Gly-TCC-010：SEQ ID No.2；
tRF-His-GTG-005：SEQ ID No.3。
2. the stem-loop primer for serum exosome tsRNA markers according to claim 1, characterized in that:
the stem-loop primer of tRF-Glu-TTC-009 is SEQ ID No. 4;
the stem-loop primer of the tRF-Gly-TCC-010 is SEQ ID No. 5;
the stem-loop primer of the tRF-His-GTG-005 is SEQ ID No. 6.
3. Primers for serum exosome tsRNA markers according to claim 1, characterized in that:
the forward primer of tRF-Glu-TTC-009 is SEQ ID No. 7;
the forward primer of the tRF-Gly-TCC-010 is SEQ ID No. 8;
the forward primer of the tRF-His-GTG-005 is SEQ ID No. 9;
the reverse primer is a universal primer sequence, and the sequence of the reverse primer is shown as SEQ ID No. 10.
4. Use of the serum exosome tsRNA marker of claim 1 in the preparation of a breast cancer diagnostic kit.
5. Use of the primers for serum exosome tsRNA markers according to claim 2 in the preparation of a breast cancer diagnostic kit.
6. Use of a stem-loop primer of a serum exosome tsRNA marker according to claim 3 in the preparation of a breast cancer diagnostic kit.
7. A breast cancer diagnostic kit characterized by: the kit is used for detecting the expression level of the tsRNA marker in the serum exosome according to claim 1.
8. The breast cancer diagnostic kit according to claim 5, wherein: the kit contains a serum Exosome Isolation reagent, which is Total Exosome Isolation (from serum) from life corporation (Invitrogen).
9. The breast cancer diagnostic kit according to claim 5, wherein: the kit contains the primer according to claim 2 and/or claim 3.
10. The breast cancer diagnostic kit according to claim 5, wherein: the breast cancer diagnostic kit also comprises AMV reverse transcriptase, dNTP, buffer solution, MgCl2, Taq enzyme, DEPC water and the like.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110810191.8A CN113416784A (en) | 2021-07-18 | 2021-07-18 | Serum exosome tsRNA marker related to breast cancer diagnosis and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110810191.8A CN113416784A (en) | 2021-07-18 | 2021-07-18 | Serum exosome tsRNA marker related to breast cancer diagnosis and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113416784A true CN113416784A (en) | 2021-09-21 |
Family
ID=77721186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110810191.8A Pending CN113416784A (en) | 2021-07-18 | 2021-07-18 | Serum exosome tsRNA marker related to breast cancer diagnosis and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113416784A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113999848A (en) * | 2021-10-25 | 2022-02-01 | 中南大学湘雅三医院 | tsRNA molecule and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106916885A (en) * | 2017-01-13 | 2017-07-04 | 青岛大学 | For detecting cardiopathic piRNA combinations and its applying |
| CN109414451A (en) * | 2016-05-16 | 2019-03-01 | 德克萨斯大学系统董事会 | For the composition and its application method as nanoparticle delivering tRNA |
-
2021
- 2021-07-18 CN CN202110810191.8A patent/CN113416784A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109414451A (en) * | 2016-05-16 | 2019-03-01 | 德克萨斯大学系统董事会 | For the composition and its application method as nanoparticle delivering tRNA |
| CN106916885A (en) * | 2017-01-13 | 2017-07-04 | 青岛大学 | For detecting cardiopathic piRNA combinations and its applying |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113999848A (en) * | 2021-10-25 | 2022-02-01 | 中南大学湘雅三医院 | tsRNA molecule and application thereof |
| CN113999848B (en) * | 2021-10-25 | 2023-06-23 | 中南大学湘雅三医院 | tsRNA molecule and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111826444B (en) | Serum/plasma tsRNA marker related to pancreatic cancer, probe and application thereof | |
| CN105671181B (en) | Gene marker, primer, probe and kit for detecting lung cancer | |
| WO2020034543A1 (en) | Marker for breast cancer diagnosis and screening method therefor | |
| CN108660215B (en) | Application of reagent for detecting circMAN1A2 and circRNF13 and kit | |
| WO2020015621A1 (en) | Method for constructing platelet nucleic acid library for gene detection and kit | |
| CN108624691A (en) | A kind of marker and its application for judging prostatic disorders | |
| CN108531586A (en) | A kind of relevant cycle miRNA marker and its application on X chromosome of and Computer-aided Diagnosis of Breast Cancer | |
| CN113337613B (en) | Serum exosome tsRNA marker related to liver cancer, probe and application thereof | |
| CN117568481A (en) | Group of plasma exosome tsRNAs markers related to liver cancer and application thereof | |
| CN113416784A (en) | Serum exosome tsRNA marker related to breast cancer diagnosis and application thereof | |
| WO2019117257A1 (en) | Method for assisting in detection of breast cancer | |
| CN110305953B (en) | Application of system for detecting miRNA expression quantity in preparation of products for distinguishing tubercular meningitis and viral meningitis | |
| CN108660213B (en) | Application of reagent for detecting three non-coding RNAs and kit | |
| CN112501295B (en) | MiRNA combination, kit containing same and application of miRNA combination in lung cancer diagnosis | |
| CN106636440B (en) | Blood plasma microRNAs is used to prepare the purposes of the diagnostic reagent of patients with lung adenocarcinoma in sieving and diagnosis male population | |
| CN115261476A (en) | Method for screening serum exosome LncRNA HULC as liver cancer early marker and application of kit prepared by method | |
| CN108823308B (en) | Application of reagent for detecting circMAN1A2 and LOC284454 and kit | |
| CN104946751B (en) | BRCA1 genes are g.41244291delT mutated and its application in Computer-aided Diagnosis of Breast Cancer | |
| CN104962612B (en) | G.41256139delT, BRCA1 gene frameshift mutation and its is preparing the application in Computer-aided Diagnosis of Breast Cancer kit | |
| CN102021169A (en) | Serum/plasma miRNA composition and use thereof | |
| CN107904309B (en) | It is a kind of for diagnose indication three negative type breast cancers Bone tumours gene diagnosis kit | |
| WO2019095541A1 (en) | Composition and method for diagnosing and predicting breast cancer bone metastases | |
| CN107460234B (en) | Application of serum 48-lncRNA as liver chronic disease diagnosis marker | |
| CN114134231B (en) | Brain glioma gene marker based on ecDNA and application thereof | |
| CN116162705B (en) | Gastric cancer diagnosis product and diagnosis model |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |