CN106191275A - The application in diagnosis three female breast carcinoma of a kind of compositions - Google Patents
The application in diagnosis three female breast carcinoma of a kind of compositions Download PDFInfo
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- CN106191275A CN106191275A CN201610590745.7A CN201610590745A CN106191275A CN 106191275 A CN106191275 A CN 106191275A CN 201610590745 A CN201610590745 A CN 201610590745A CN 106191275 A CN106191275 A CN 106191275A
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- 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
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- 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
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- 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 present invention proposes the application in diagnosis three female breast carcinoma of a kind of compositions, described compositions is miR 141, miR 200a and miR 145, and the present invention confirms that gene miR 141, miR 200a and miR 145 combine first and mainly lowers at three female breast carcinomas.In three Breast Cancer Patients with Negative Axillary serum, also the blood serum of patients with human breast carcinoma of relatively other molecule partings substantially reduces simultaneously.The present invention is not only breast cancer molecular typing and provides new data, and the detection for the negative molecule parting of breast carcinoma three provides new target spot and a serology method for quick.
Description
Technical field
The present invention relates to the biomarker of breast carcinoma, be specifically related to a kind of compositions answering in diagnosis three female breast carcinoma
With.
Background technology
One of malignant tumor that breast carcinoma number most common in being currently global range, lethal is most, its sickness rate and dead
Rate of dying rapid development.The mortality rate of breast cancer patients to be reduced, in addition to reducing sickness rate on causal prophylaxis, improves and examines in early days
The curative effect of gentle Drug therapy of cutting off the water supply is two importances.But, the early diagnosis of pulmonary carcinoma is always a global problem,
Diagnostic imaging (B ultrasonic, molybdenum target) at present, chemical diagnosis (cancer reaction, serology and amynologic index) and histocytology diagnosis are
The big pillar of the three of diagnosing tumor, the former has the biggest limitation on Patients with Subclinical diagnoses, the latter two all using tumor markers as
Observation index, can find the existence of tumor earlier than diagnostic imaging, have efficiently, high sensitivity, convenience, specimen easily obtain and
The advantages such as wound is little, therefore, in the breast carcinoma research of diagnosis and treatment in early days, screen and identify the breast cancer tumour mark of high specific
The emphasis always studied and difficult point.
So-called tumor markers, refers to occur and in breeding in tumor, by tumor cell biosynthesis, release or
The class material that to be tumor interact with host and produces, reflects existence and the growth of tumor.We can be by utilization
The technology such as, immunity, molecular biology carry out qualitative or quantitative detection to blood or secretions, by it is analyzed, and side
Us are helped to distinguish tumor from normal structure or measure neoplastic cell nuclei, Cytoplasm and the characteristic on cell membrane carried out point
Analysis, in this, as the mark distinguishing tumor cell.The generation of breast carcinoma has sufficiently complex mechanism with development, and it is fallen ill
Just the stage relates to many breast cancer related genes and the change of expression thereof, can express in the patient under the effect of carcinogenic factor
Various adhesion molecules and receptor thereof or part, the most different at its release mark thing content of different times of tumor development.
According to ER, PR, HER2 type of SABC detection and the result of Ki67, breast carcinoma can be divided into 4 at present
Type, i.e. Luminal A type, Luminal Type B, HER2 type and basal type.Wherein Luminal A type is that breast carcinoma is most common
Molecular isoform.Although breast carcinoma has reasonable molecule parting at present, but this molecule parting is to detect based on breast cancer tissue,
And can not be as the tracking of Prognosis in Breast Cancer effect.
And due to multiformity, the heterogeneity of pathology tumor cell of the same race and the tumor biological behavior of breast cancer tissue's pathology
Complexity and polymorphism, cause unique identification analyte detection limited to the diagnostic value of breast carcinoma, can only reflect disease some
The change of side, lot of domestic and foreign scholar tends to screen multiple valuable tumor markers and carries out joint-detection, to improve
The positive rate of breast cancer diagnosis.Although joint-detection is better than individual event detection has become common recognition, but not any one combination all can carry
The positive rate of high clinical diagnosis, on best of breed, conclusion is the most inconsistent, contrary result even occurs.Therefore, find also
The compositions and the effect thereof that solve a kind of biomarker being applied to breast carcinoma clinical diagnosis and treatment have become breast cancer research
One of middle problem demanding prompt solution.
Summary of the invention
In view of this, it is an object of the invention to propose a kind of can more accurate expression microRNA in breast carcinoma
The application of effect, the application in diagnosis three female breast carcinoma of a kind of compositions.
The technical scheme used is:
A kind of compositions diagnosis three female breast carcinoma in application, described compositions be miR-141, miR-200a and
MiR-145, said composition is lowered at three female breast carcinomas.
Further, miR-in three negative breast cancer cells system MDA-MB-231, BT-549, SUM1315 and Hs578T
141, miR-200a and miR-145 compositions expression is significantly lower than Luminal type MCF7, T47D and BT474 cell line, with
And HER2 process LAN type SKBR3 cell line, and less than normal mammary epithelial HMLE.
Further, compared to the Carcinoma side normal tissue of pairing, miR-141, miR-200a and miR-145 compositions is three
Expression in female breast cancer tissue is significantly lower than Luminal type breast cancer tissue.
Further, compared to normal galactophore tissue, Luminal A type breast cancer tissue, Luminal Type B breast carcinoma group
Knitting and HER2 positive type breast cancer tissue, miR-141, miR-200a and miR-145 compositions is in three female breast cancer tissues
Express and substantially lower.
Further, suffer from compared to normal human serum, Luminal A type, Luminal Type B and HER2 positive type breast carcinoma
Person's serum, in three female blood serum of patients with human breast carcinomas, miR-141, miR-200a and miR-145 compositions level is substantially lowered.
Further, in three female breast cancer cell MDA-MB-231 and BT549 cell simultaneously process LAN miR-141,
After miR-200a and miR-145 compositions, the upper table mark E-cadherin up-regulated of cell, and interstitial mark
Snail1, Vimentin and N-cadherin down-regulated expression, the invasive ability of cell reduces simultaneously.
Further, in three female breast cancer cell MDA-MB-231 and BT549 cell simultaneously process LAN miR-141,
After miR-200a and miR-145 compositions, the breast carcinoma stem cell ratio of CD44+/CD24-substantially reduces, and uses stem cell simultaneously
Spheroid culture experiment also finds that the spheroid Forming ability of cell reduces.
Further, simultaneously after process LAN miR-141, miR-200a and miR-145 compositions, can substantially suppress corresponding swollen
The growth of tumor, and increase chemosensitivity
The beneficial effects of the present invention is:
The present invention confirms gene miR-141, miR-200a and miR-145 compositions table in three female breast carcinoma first
Reaching downward, the most only breast cancer molecular typing provides new data, and the detection for the negative molecule parting of breast carcinoma three carries
New target spot and a serology method for quick are supplied.
The compositions of the present invention is down-regulated expression in three female breast cancer tissues and patients serum, can be as three female mammary gland
The serodiagnostic markers of cancer, and compositions can suppress the progress of three female breast carcinoma and increase chemosensitivity, therefore simultaneously can
The Serologic detection mark passed judgment on is followed the trail of as three female patient with breast cancer's prognosis.
Accompanying drawing explanation
Fig. 1-Fig. 3 is the experimental result picture in embodiment 1；
Fig. 4 is the experimental result picture in embodiment 2；
Fig. 5 is the experimental result picture in embodiment 3；
Fig. 6-Fig. 8 is the experimental result picture in embodiment 4；
Fig. 9-Figure 11 is the experimental result picture in embodiment 5；
Figure 12-14 is the experimental result picture in embodiment 6；
Figure 15-Figure 19 is the experimental result picture in embodiment 7.
Detailed description of the invention
Below in conjunction with accompanying drawing, the present invention is clearly and completely described further.
Embodiment 1
Use the detection of miRNA specific PCR, i.e. extract cell miRNAs and after reverse transcription, examine with real-time quantitative PCR
Surveying, testing result sees shown in Fig. 1-Fig. 3, it was found that at three negative breast cancer cells system MDA-MB-231, BT-549,
In SUM1315 and Hs578T, miR-141, miR-200a and miR-145 expression is significantly lower than Luminal type MCF7, T47D
With BT474 cell line, and HER2 process LAN type SKBR3 cell line, and less than normal mammary epithelial HMLE.
Embodiment 2
After linked groups being taken out from liquid nitrogen and make tissue homogenate, extracting organizes miRNAs and after reverse transcription, uses
Real-time quantitative PCR detects, and uses miRNA specificity qRT-PCR detection 72 to normally matching breast cancer tissue by cancer and cancer
MiR-141, miR-200a and miR-145 expression in (Luminal type 43 example, three female 29 examples), testing result sees Fig. 4
Shown in, found that compared to the Carcinoma side normal tissue of pairing, miR-141, miR-200a and miR-145 are in three female breast carcinoma
(TNBC) expression in tissue is significantly lower than Luminal type breast cancer tissue.
Embodiment 3
With miRNA specificity hybridization in situ technique (ISH, insituhybridizations, purpose miRNAs dye blueness,
Nuclei dyeing is red) detect miR-141, miR-200a and miR-145 expression in breast cancer tissue, testing result sees Fig. 5 institute
Show, it was found that compared to normal galactophore tissue, Luminal A type breast cancer tissue, Luminal Type B breast cancer tissue and
HER2 positive type breast cancer tissue, miR-141, miR-200a and miR-145 three female expression in breast substantially under
Adjust.
Embodiment 4
Enrichment extracting 30 example normal human serums, 34 example Luminal A types, 47 example Luminal Type Bs, 26 example HER2 positive types
And 32 example three female breast cancer serum miRNAs, with exogenous cel-miR-67 as reference, examine with miRNA specificity qRT-PCR
Surveying miR-141, miR-200a and miR-145 level in serum, testing result sees shown in Fig. 6-Fig. 8, it was found that compared to
Normal human serum, Luminal A type, Luminal Type B and HER2 positive type blood serum of patients with human breast carcinoma, three female patient with breast cancers
In serum, miR-141, miR-200a and miR-145 level is substantially lowered.
Embodiment 5
See shown in Fig. 9-11, the process LAN while of in three female breast cancer cell MDA-MB-231 and BT549 cell
After miR-141, miR-200a and miR-145, western blot detection finds the upper table mark E-cadherin table of cell
Reach rise, and interstitial mark Snail1, Vimentin and N-cadherin down-regulated expression, meanwhile, transwell experimental result
The invasive ability of prompting cell reduces.
Embodiment 6
See shown in Figure 12-Figure 14, the process LAN while of in three female breast cancer cell MDA-MB-231 and BT549 cell
After miR-141, miR-200a and miR-145, find that with flow cytometer detection the breast carcinoma stem cell ratio of CD44+/CD24-substantially drops
Low, also find that the spheroid Forming ability of cell reduces by stem cell spheres culture experiment simultaneously.
Embodiment 7
Shown in Figure 15-Figure 19, by while process LAN miR-141, miR-200a and miR-145 MDA-MB-231 and
After BT549 cell and corresponding compared with control cells inoculation nude mice thereof, within 21 days, start that to give lumbar injection same volume respectively raw become tumor
Reason saline (100ul), 5-Fu (30mg/kg) or Paclitaxel (15mg/kg), every three days once, shares medicine 6 times, every three days
The diameter of measurement tumor, to calculate gross tumor volume and to draw tumor growth curve, is finally peeled away tumor body and weighs, finding mistake simultaneously
Express miR-141, miR-200a and miR-145 and can substantially suppress the growth of corresponding tumor, and increase chemosensitivity.
The a series of detailed description of those listed above is only for illustrating of the possible embodiments of the present invention,
They also are not used to limit the scope of the invention, all Equivalent embodiments made without departing from skill of the present invention spirit or change
Should be included within the scope of the present invention.
Claims (8)
1. the compositions application in diagnosis three female breast carcinoma, it is characterised in that described compositions be miR-141,
MiR-200a and miR-145, said composition is lowered at three female breast carcinomas.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that negative three
MiR-141, miR-200a and miR-145 combination in breast cancer cell line MDA-MB-231, BT-549, SUM1315 and Hs578T
Thing expression is significantly lower than Luminal type MCF7, T47D and BT474 cell line, and HER2 process LAN type SKBR3 cell
System, and less than normal mammary epithelial HMLE.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that compared to joining
To Carcinoma side normal tissue, the expression in three female breast cancer tissues of miR-141, miR-200a and miR-145 compositions is bright
Aobvious less than Luminal type breast cancer tissue.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that compared to just
Often mammary gland tissue, Luminal A type breast cancer tissue, Luminal Type B breast cancer tissue and HER2 positive type breast cancer tissue,
MiR-141, miR-200a and miR-145 compositions is substantially lowered in three female expression in breast.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that compared to just
Ordinary person's serum, Luminal A type, Luminal Type B and HER2 positive type blood serum of patients with human breast carcinoma, three female blood of patients with breast cancers
In clear, miR-141, miR-200a and miR-145 compositions level is substantially lowered.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that in three female
The while of in breast cancer cell MDA-MB-231 and BT549 cell after process LAN miR-141, miR-200a and miR-145 compositions,
The upper table mark E-cadherin up-regulated of cell, and interstitial mark Snail1, Vimentin and N-cadherin table
Reaching downward, the invasive ability of cell reduces simultaneously.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that in three female
The while of in breast cancer cell MDA-MB-231 and BT549 cell after process LAN miR-141, miR-200a and miR-145 compositions,
The breast carcinoma stem cell ratio of CD44+/CD24-substantially reduces, and also finds the ball of cell by stem cell spheres culture experiment simultaneously
Body Forming ability reduces.
The compositions the most according to claim 1 application in diagnosis three female breast carcinoma, it is characterised in that simultaneously cross table
After reaching miR-141, miR-200a and miR-145 compositions, can substantially suppress the growth of corresponding tumor, and increase chemosensitivity
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107227354A (en) * | 2017-06-16 | 2017-10-03 | 清华大学深圳研究生院 | A kind of diagnosis marker related to breast cancer and application thereof |
| CN109825592A (en) * | 2019-04-15 | 2019-05-31 | 德阳市人民医院 | A kind of purposes of biomarker relevant to breast cancer occurrence and development |
-
2016
- 2016-07-25 CN CN201610590745.7A patent/CN106191275A/en active Pending
Non-Patent Citations (3)
| Title |
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| 杜娟等: "三阴乳腺癌的特点及研究进展", 《首都医科大学学报》 * |
| 赵晓艾等: "三阴性乳腺癌差异表达miRNA的筛选", 《西安交通大学学报(医学版)》 * |
| 郑国沛: "旁分泌或自分泌细胞因子在乳腺癌上皮-间质转化(EMT)及耐药和转移中的作用", 《中国博士学位论文全文数据库医药卫生科技辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107227354A (en) * | 2017-06-16 | 2017-10-03 | 清华大学深圳研究生院 | A kind of diagnosis marker related to breast cancer and application thereof |
| CN109825592A (en) * | 2019-04-15 | 2019-05-31 | 德阳市人民医院 | A kind of purposes of biomarker relevant to breast cancer occurrence and development |
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Application publication date: 20161207 |