CN103160509B - miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and application - Google Patents
miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and application Download PDFInfo
- Publication number
- CN103160509B CN103160509B CN201310073210.9A CN201310073210A CN103160509B CN 103160509 B CN103160509 B CN 103160509B CN 201310073210 A CN201310073210 A CN 201310073210A CN 103160509 B CN103160509 B CN 103160509B
- Authority
- CN
- China
- Prior art keywords
- prognosis
- primer
- seq
- esophageal carcinoma
- mir
- 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.)
- Active
Links
Abstract
The invention discloses a miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and an application, wherein, the miRNA marker is has-miR-212. The invention relates to an application of the miRNA marker in preparation of a kit for esophagus cancer postoperative early relapse and prognosis auxiliary diagnosis. The invention relates to an application of a primer of the miRNA marker relative to esophagus cancer postoperative early relapse and prognosis in preparation of the kit for esophagus cancer postoperative early relapse and prognosis auxiliary diagnosis. The invention relates to the primer of the miRNA marker relative to esophagus cancer postoperative early relapse and prognosis in preparation of the kit for esophagus cancer postoperative early relapse and prognosis auxiliary diagnosis. The method provided by the invention is simple, the operation is convenient, the screened has-miR-212 can determine the prognosis or death risk of the patients in an auxiliary mode, and the development for diagnosis and treatment of the esophagus cancer can be promoted.
Description
Technical field
The present invention relates to a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma, also relate to the application of this mark simultaneously, belong to genetically engineered and oncology.
Background technology
The esophageal carcinoma (Esophageal carcinoma, EC) be common malignant tumor of digestive tract, account for the second of each region tumors death of Digestive tract, the whole world is died from this disease every year and is reached 300,000 people, wherein annual Mean Death about 150,000 people of China, is the country that Incidence of esophageal cancer is the highest in the world.Although achieve greater advance in recent years in the chemotherapy, radiotherapy and Role of Concurrent Chemoradiotherapy etc. of the esophageal carcinoma, surgical operation is still the topmost treatment means of the esophageal carcinoma so far.But result for the treatment of is undesirable, within 5 years, survival rate is only about 30%, and main causes of death are postoperative recurrence and transfer, especially the nodus lymphoideus transferring rate of patient with esophageal carcinoma early postoperation.At present both at home and abroad the recurrence of its early postoperation of report and the rate of transform (in postoperative 1 year) can not reach about 20-50% not etc., and this is all heavy blows to the confidence of patient and surgeon, and some patients is even to surgery operative effect generation query.Natural history or the title of patient with esophageal carcinoma are about the 6-12 month lifetime, occur early stage recurrence and transfer, mean the failure of operation, take chemicotherapy more useful in other words to these patients in postoperative 1 year.
The factor affecting esophageal carcinoma prognosis is a lot, judges the main method of esophageal carcinoma prognosis or traditional Tumor Nodemetastasis (TNM) method by stages at present.In the clinical diagnosis and treatment process of the esophageal carcinoma, classical TNM pathological staging system for different pathological by stages Index for diagnosis play an important role, but for the pathological staging run in clinical position is identical, the obvious situation of prognosis difference cannot be explained, and lacks the judgement effect of recurring in early days postoperative appearance.At present, clinical workers is improving TNM Staging System further with evaluate its prognosis.Meanwhile, basic medical personnel also considers from Tumor Heterogeneity aspect difference, finds the molecular indexes of new judging prognosis, as the useful supplement of TNM pathological staging system.Relate to the sudden change of multiple oncogene, cancer suppressor gene in the generation of the esophageal carcinoma, evolution, produce the change of various zymetology, show as the synergy of polygene, multifactor, multi-step.Research for the esophagus cancer diagnosis molecular biology mark relevant with prognosis becomes research emphasis.
The research of current esophageal carcinoma tumor molecular marker and report more, except the tumor marker carcinomebryonic antigen (CEA) of traditional sense, squamous cell cancer related antigen (SCC), cellular keratinization fibroin fragment 19(CYFRA2l – l), beyond p53 protein antibodies (p53-Ab) etc., focus molecular marked compound EGFR(EGF-R ELISA in current research), CycIinDl(Cyclin D1 l), COX-2(cyclooxygenase 2), PCNA(proliferating cell nuclear antigen), VEGF(vascular endothelial growth factor) etc. all have certain clinical meaning to esophageal carcinoma Index for diagnosis, but above molecular marked compound mainly concentrates on the research to different pathologic stages of tumour, and to nodus lymphoideus transferring rate, the impact of the single factor such as tumor invasive depth, lack identical pathological staging, same patient, identical art formula, identical aftertreatment scheme and the research of prognosis different molecular labels, lack research Thoracic esophageal carcinoma being occurred to early stage recurrence and transfer, lack specificity and the high molecular marked compound of susceptibility to predict the generation of the esophageal carcinoma, development and prognosis, and esophageal canceration and evolution are the results that polygene changes, the change of its molecular biology is also incomplete same, associating molecular marked compound detects the susceptibility contributing to improving judging prognosis.
The endogenous non-coding regulatory RNA of microRNAs(miRNAs) to be a class length be twenties Nucleotide, carry out regulate gene expression by sequence-specific Translational repression or mRNA cracking, participate in a series of important biomolecule processes such as cell development, propagation, differentiation, apoptosis.Recent research finds, miRNA has the effect of oncogene and cancer suppressor gene, plays an important role in the generation and development of tumour.If the miRNA filtering out the special or unconventionality expression of the early stage recurrence and prognosis of Thoracic esophageal carcinoma is as biomarker, and develop the monitoring of corresponding progression of disease, auxiliary diagnostic box, will be once strong promotion to the current diagnosis and treatment of our esophageal carcinoma, especially avoid unnecessary surgical operation to have great significance to some patients.In addition, the miRNA of these unconventionality expressions, for the impact etc. of esophageal cancer cell migration, transfer ability, also contributes to the new small molecule medicine finding to have potential therapeutic value.
Summary of the invention
The object of this invention is to provide a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma.
In order to realize above object, the technical solution adopted in the present invention is to provide a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma, and described miRNA marker is has-miR-212.
The primer of described miRNA marker is as shown in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6.
The present invention also aims to provide a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma preparing the application in Thoracic esophageal carcinoma early stage recurrence and prognosis auxiliary diagnostic box.
The technical solution adopted in the present invention is also to provide a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma preparing the application in Thoracic esophageal carcinoma early stage recurrence and prognosis auxiliary diagnostic box.
Described test kit comprises the primer of has-miR-212, pcr reagent, U6snRNA internal reference primer and fluorescence dye SYBR-Green1.
The present invention also aims to provide a kind of primer of the miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma preparing the application in Thoracic esophageal carcinoma early stage recurrence and prognosis auxiliary diagnostic box.
The technical solution adopted in the present invention is also to provide a kind of primer of the miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma preparing the application in Thoracic esophageal carcinoma early stage recurrence and prognosis auxiliary diagnostic box.
The present invention also aims to the Thoracic esophageal carcinoma early stage recurrence and prognosis auxiliary diagnostic box of the primer that a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma is provided.
The technical solution adopted in the present invention is also the Thoracic esophageal carcinoma early stage recurrence and prognosis auxiliary diagnostic box of the primer providing a kind of miRNA marker relevant to the early stage recurrence and prognosis of Thoracic esophageal carcinoma.
The reagent provided in this test kit is provided, extracts reagent and general miRNA reverse transcription reagents in conjunction with conventional RNA, the expression amount of has-miR-212 in tissue can be detected specifically, effectively for the auxiliary diagnosis of the clinical esophageal carcinoma.
The screening method of has-miR-212 of the present invention, comprises the following steps:
1, select identical pathological staging, typical sample that same patient, identical art formula, identical aftertreatment scheme but have completely different prognosis, choose the normal esophageal mucous membrane product in contrast beyond pathological staging same distance tumor tissues edge 8cm simultaneously;
2, the RNA of sample and reference substance is extracted;
3, by reverse transcription, cDNA is obtained to total serum IgE;
4, cDNA increases in advance;
5, pre-amplified production is carried out real-time fluorescence RT-PCR amplification, the miRNA that there is notable difference is expressed in screening, carries out the expression statistical study of miRNA, and screening obtains the relevant miRNA marker of recurrence and prognosis early stage to Thoracic esophageal carcinoma.
The present invention chooses the tumor sample and the contrast of normal esophageal setup action thereof that postoperative recurrence of esophageal cancer time and prognosis differ greatly, by extracting RNA, the miRNA that there is notable difference is expressed in the screening of reverse transcription, real-time fluorescence quantitative RT-PCR, carry out the expression statistical study of miRNA, screening obtains has-miR-212.The inventive method is simple, easy to operate, and screening the has-miR-212 that obtains can the prognosis of auxiliary judgment patient with esophageal carcinoma or mortality risk, has promoted the development of esophageal carcinoma diagnosis and treatment aspect.
The miRNA test kit adopting the present invention to prepare, not only stablizes, easy to detect, and quantitatively accurate, greatly improves the Sensitivity and Specificity of medical diagnosis on disease, this test kit is dropped into practice, can assisted diagnosis and more effective individualized treatment.
Accompanying drawing explanation
Fig. 1 is that pathological staging is identical, prognosis difference patient with esophageal carcinoma expresses RT-PCR amplification curve to has-miR-212;
Fig. 2 is the MELD methods analysis chart of has-miR-212 expression amount and esophageal carcinoma prognosis.
Embodiment
Embodiment
1, the selection of sample
Choose the pathological staging that The First Affiliated Hospital of Xinxiang Medical University 2006-2007 accepts for medical treatment identical, 2 routine paraffin specimens of prognosis existence notable difference, the paraffin specimen that the first operation tumor resection sample that this 2 routine sample is primary lesion makes.Normal esophageal mucous membrane simultaneously respectively beyond this 2 routine paraffin sample tumor tissues edge 8cm of selected distance in contrast.2 routine cases, preoperative through the physical examination of whole body physics and imaging diagnosis without distant metastasis, preoperatively do not accept radiotherapy or chemotherapy etc., all adopt Resection Esophagus Carcinoma+chest abdomen two-field lymphadenectomy, neck is manual to coincide, postoperative chemotherapy 2 times, postoperative pathological checks prompting Esophageal Middle Segment differentiated squama cancer, ulcer type, invade and adventitia, without nodus lymphoideus transferring rate, according to International Union Against Cancer (UICC) sixth version staging scale in 2002, 2 examples are T3N0M0, clinical stages was II a phase, but there is notable difference in prognosis, one example is still still living and in good health for postoperative 5 years, one example postoperative 4 months metastasic cervical lymph nodes, 1 year dead.
2, RNA is extracted
1) adopt Trizol single stage method to extract total serum IgE in the micro-cutting tumour cell of paraffin-embedded tissue, operate and extract test kit (Invitrogen, USA) according to RNA and illustrate and carry out.
2) reclaim total serum IgE, operate according to Recover All Total Nucleic Acid Isolation Kit TRIZOL REAGENT(Ambion, USA) specification sheets carry out.
3) adopt point tube photometer to measure the photoabsorption angle value at wavelength 230,260,280nm place respectively, determine purity and the concentration of total serum IgE.
4) denaturing formaldehyde agarose gel electrophoresis detects the ratio of 28s and 18s in total serum IgE sample, identifies its purity and integrity.
3, Megaplex reverse transcription
A) Megaplex reverse transcription system is as shown in table 1.
Table 1Megaplex reverse transcription system
| Component | Add-on |
| Reverse transcriptase primer (10 ×) | 0.8μL |
| dNTPs with dTTP(100mM) | 0.2μL |
| MultiScribe TMReversed transcriptive enzyme (50U/ μ L) | 1.5μL |
| 10 × RT Buffer | 0.8μL |
| MgCl 2(25mM) | 0.9μL |
| RNA enzyme inhibitors (20U/ μ L) | 0.1μL |
| Nuclease free water | 0.2μL |
| Cumulative volume | 4.5μL |
Reverse transcription system is put upside down 6 mixings, slightly centrifugal; Add 3 μ L total serum IgE again in reaction tubes, it is centrifugal to put upside down 6 mixings, places 5min on ice.
B) reverse transcription reaction condition is as shown in table 2.
Table 2 reverse transcription reaction condition
After having reacted, reverse transcription product is placed in for subsequent use on ice.
4, increase in advance
1) PCR reaction system is as shown in table 3.
Table 3PCR reaction system
Reaction system is put upside down 6 times, slightly centrifugal, place 5min on ice.
2) PCR reaction conditions is as shown in table 4.
Table 4PCR reaction conditions
0.1 × TE(pH8.0 is added in the reaction tubes of table 4) 75 μ L, put upside down 6 mixings, ﹣ 20 DEG C preservation.
5, real-time fluorescence quantitative RT-PCR
1) whirlpool mixing
universal PC R pre-mixed PCR reaction solution.
2) PCR reaction system is as shown in table 5.
Table 5PCR reaction system
The reaction system of table 5 is put upside down 6 mixings, centrifugal.
3) in each hole of Taqman MicroRNA Array, 100 μ L PCR reaction mixtures are added, centrifugal 2 times of 1200rpm, each 1min.
4) pcr amplification program is as shown in table 6.
Table 6PCR amplification program
6, real-time fluorescence quantitative RT-PCR interpretation of result
Using U6snRNA house-keeping gene as internal reference, adopt relative quantification method, calculate the expression amount of gene.
The expression amount F=2 of gene
-△ △ ct
The larger expression amount of F value is higher.Wherein, the mean value of the ct of the house-keeping gene of the mean value-sample to be tested of the ct of the goal gene of △ △ ct=(testing sample)-(mean value of the ct of the house-keeping gene of the mean value-check sample of the ct of the goal gene of control sample).
To all detecting that in three samples miRNA expresses, and the miRNA marker of ct value between 10-28 is analyzed.Found that, there is notable difference in the gene expression amount of gene expression amount in 2 routine samples of has-miR-212.Compared with the sample dead with Thoracic esophageal carcinoma 1 year, prognosis is poor, has-miR-212 is alive Thoracic esophageal carcinoma 5 years, the good sample of prognosis is lowered, and expression amount is 11.661, expression amount 24.139 in the sample that prognosis is poor, lowers 2.070 times.
Experimental example 1, has-miR-212 are in the by stages identical and checking of prognosis difference patient with esophageal carcinoma differential expression
1, the selection of sample
Choose the pathological staging that The First Affiliated Hospital of Xinxiang Medical University 2006-2009 accepts for medical treatment identical, 46 routine paraffin specimens of prognosis existence notable difference, the paraffin specimen that the first operation tumor resection sample being primary lesion makes; Preoperative through whole body physics physique inspection machine imaging diagnosis without distant metastasis, preoperatively do not accept radiotherapy or chemotherapy etc.Wherein 18 examples are postoperative 5 years alive, the good esophageal carcinoma samples of prognosis, and 28 examples are the poor esophageal carcinoma sample of recurrence in early days in postoperative 1 year, prognosis, and patient data is in table 7.Choose normal esophageal mucous membrane beyond pathological staging same distance tumor tissues edge 8cm in contrast simultaneously.
The routine patient with esophageal carcinoma clinical data of table 746
2, RNA is extracted
Extracting method is with the extracting method in embodiment 1.
3, Megaplex reverse transcription
Reverse transcriptase primer is according to obtaining has-miR-212 mature sequence (MIMAT0022695) in miRBaSe database: 5 '-ACCUUGGCUCUAGACUGCUUACU-3 ' design, as follows:
Reverse transcriptase primer 1:5 '-CTCAACTGGTGTCGTGGAGTCGGCAATTCAGTTGAGACTAAG-3 ' (SEQ ID NO:1)
Reverse transcriptase primer 2:5 '-CTCAACTGGTGTCGTGGAGTCGGCAATTCAGTTGAGACTAAGC-3 ' (SEQ ID NO:2)
Reverse transcriptase primer 3:5 '-CTCAACTGGTGTCGTGGAGTCGGCAATTCAGTTGAGACTAAGA-3 ' (SEQ ID NO:3)
U6snRNA reverse primer: 5 '-AACGCTTCACGAATTTGCGT-3 '
Reverse transcription reaction system (20 μ L): 5 × primer buffer4 μ L, reversed transcriptive enzyme 1 μ L, reverse transcriptase primer 1(10 μM) 0.5 μ L, U6snRNA reverse primer (10 μMs) 0.5 μ L, RNA1 μ g, add and mend to 20 μ L systems without RNA enzyme water.
Reverse transcription reaction condition: 42 DEG C of incubation 15min, 85 DEG C of deactivation reversed transcriptive enzyme 5s, 4 DEG C of preservations.
Reverse transcriptase primer 2,3 carries out reverse transcription reaction with reverse transcription 1.
4, real-time fluorescence quantitative RT-PCR
According to obtaining has-miR-212 mature sequence (MIMAT0022695) in miRBaSe database: 5 '-ACCUUGGCUCUAGACUGCUUACU-3 ' designs the primer of real-time fluorescence quantitative RT-PCR, as follows:
Forward primer 1:5 '-ACACTCCAGCTGGGACCTTGGCTCTAGACT-3 ' (SEQ ID NO:4)
Forward primer 2:5 '-ACACTCCAGCTGGGACCTTGGCTCTAGACTGC-3 ' (SEQ ID NO:5)
General reverse primer: 5 '-TGGTGTCGTGGAGTCG-3 ' (SEQ ID NO:6)
The reaction system (20 μ L) of fluorescence quantitative RT-RCR: 2 × SYBR Green PCR Master Mix10 μ L, template cDNA1 μ L, forward primer and each 0.5 μ L of reverse primer (10 μMs), distilled water is settled to 20 μ L.When real time fluorescent quantitative detects, forward primer 1,2 carries out pcr amplification with general reverse primer respectively.Template cDNA is that reverse transcriptase primer 1,2,3 reverse transcription produces.
Reaction conditions is: 95 DEG C of sex change 1min, 95 DEG C of 30s, 65 DEG C of 1min, 40 circulations, and after loop ends, from 55 DEG C, every 10s rises 0.5 DEG C, gets fluorescent value and draws solubility curve, determine the specificity of amplified production.
RT-PCR amplification curve is shown in Fig. 1.
5, has-miR-212 expression amount statistical study
Using U6snRNA house-keeping gene as internal reference, adopt relative quantification method, calculate the expression amount of gene.
The expression amount F=2 of gene
-△ △ ct
The larger expression amount of F value is higher.Wherein, the mean value of the ct of the house-keeping gene of the mean value-sample to be tested of the ct of the goal gene of △ △ ct=(testing sample)-(mean value of the ct of the house-keeping gene of the mean value-check sample of the ct of the goal gene of control sample).
Result shows, recur in early days with Thoracic esophageal carcinoma, compared with sample that prognosis is poor, has-miR-212 is in Thoracic esophageal carcinoma alive, the good sample rise of prognosis in 5 years, it is 5.076 ± 5.744 that analytical results is presented at has-miR-212 expression amount in the good sample of prognosis, expression amount 11.139 ± 9.115 in the sample that prognosis is poor, lower 2.1944 times, difference has statistical significance, as shown in table 8.
Table 8has-miR-212 is in identical TNM esophageal carcinoma sample expression analysis result by stages
The MELD methods analyst of experimental example 2, has-miR-212 expression amount and the early stage recurrence and prognosis of Thoracic esophageal carcinoma
Kaplan-Meier is adopted to carry out correlation analysis to has-miR-212 expression amount and survival time, as shown in Figure 2.Result display has-miR-212 expression amount and survival time have significant correlation (p=0.024).
To Patients With Carcinoma of Esophagus prognosis situation, sex, age, TNM by stages, postoperative T, N0-N1 phase, tumor size, differentiation degree and has-miR-212 expression amount carry out the analysis of Cox single factor test associated risks, result is as shown in table 9.Result display patient's prognosis situation (P=0.000), TNM (P=0.023), postoperative T(p=0.010 by stages), the survival time of tumor size (p=0.006) and has-miR-212 expression amount (p=0.032) and patient has significant correlation.
The MELD method single factor analysis of table 9has-miR-212 expression amount and the early stage recurrence and prognosis of Thoracic esophageal carcinoma
Include above-mentioned relevant Hazard Factor in Cox Multiple-Factor Model to analyze, result is as shown in table 10.Result display only has patient's prognosis (p=0.002), tumor size (p=0.001) and has-miR-212 expression amount (p=0.026) and its survival time all to have significant correlation, and its hazard degree is respectively 7.405,1.399 and 2.785.
The MELD method multiplicity of table 10has-miR-212 expression amount and the early stage recurrence and prognosis of Thoracic esophageal carcinoma
Application Example, miRNA test kit
MiRNA test kit comprises has-miR-212 primer (as shown in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6), pcr reagent (comprising warm start Taq archaeal dna polymerase (2.5U/ μ L) and reaction buffer, dNTP (10mM)), U6snRNA internal reference primer and fluorescence dye SYBR-Green1.Utilize test kit of the present invention, extract reagent and general miRNA reverse transcription reagents in conjunction with conventional RNA, the expression amount of has-miR-212 in tissue can be detected specifically, effectively for the auxiliary diagnosis of the clinical esophageal carcinoma.
The effect detection of miRNA test kit:
Choose the good Patients With Carcinoma of Esophagus of the routine prognosis of The First Affiliated Hospital of Xinxiang Medical University 2008-2011 20 and the poor Patients With Carcinoma of Esophagus of 18 routine prognosis, miRNA extraction has been carried out to its paraffin specimen, miRNA test kit of the present invention is utilized to analyze sample, result shows miRNA test kit of the present invention can be special, effectively amplify has-miR-212 sequence, statistical study is carried out to its expression amount, in the good sample of result display prognosis, has-miR-212 expression amount is 5.615 ± 3.122, in the sample that prognosis is poor, has-miR-212 expression amount is 12.508 ± 5.167, the expression amount of has-miR-212 is lowered 2.227 times (P<0.05).The 20 routine prognosis good Patients With Carcinoma of Esophagus has-miR-212 expression amount detected has all poor than the prognosis expression amount of 18 examples obviously to decline, and susceptibility is 90.0%.
Claims (2)
1. the primer of a miRNA marker relevant to the postoperative early stage recurrence and prognosis of esophageal squamous cell carcinoma is preparing the application in the postoperative early stage recurrence and prognosis auxiliary diagnostic box of esophageal squamous cell carcinoma, it is characterized in that: described primer comprises reverse transcriptase primer and real-time fluorescence quantitative RT-PCR primer, reverse transcriptase primer is as shown in SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and real-time fluorescence quantitative RT-PCR primer is as shown in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6.
2. the postoperative early stage recurrence and prognosis auxiliary diagnostic box of esophageal squamous cell carcinoma of the primer containing the miRNA marker relevant to the postoperative early stage recurrence and prognosis of esophageal squamous cell carcinoma, it is characterized in that: described primer comprises reverse transcriptase primer and real-time fluorescence quantitative RT-PCR primer, reverse transcriptase primer is as shown in SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and real-time fluorescence quantitative RT-PCR primer is as shown in SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310073210.9A CN103160509B (en) | 2013-03-07 | 2013-03-07 | miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310073210.9A CN103160509B (en) | 2013-03-07 | 2013-03-07 | miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103160509A CN103160509A (en) | 2013-06-19 |
| CN103160509B true CN103160509B (en) | 2015-02-18 |
Family
ID=48584043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310073210.9A Active CN103160509B (en) | 2013-03-07 | 2013-03-07 | miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103160509B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106701992B (en) * | 2017-02-16 | 2020-11-27 | 中国人民解放军总医院 | Esophageal cancer prognosis marker and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2295604A2 (en) * | 2004-02-09 | 2011-03-16 | Thomas Jefferson University | Diagnosis and treatment of cancers with microRNA located in or near cancer-associated chromosomal features |
| CN102399870A (en) * | 2006-11-28 | 2012-04-04 | 博奥生物有限公司 | Reagent for determining survival and prognosis of patients with esophagus cancer |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013022995A2 (en) * | 2011-08-08 | 2013-02-14 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Biomarker compositions and methods |
| NZ595800A (en) * | 2009-07-14 | 2013-04-26 | Morinaga Milk Industry Co Ltd | Screening for a diet or substance that increases or decreases the amount of microrna present in milk |
-
2013
- 2013-03-07 CN CN201310073210.9A patent/CN103160509B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2295604A2 (en) * | 2004-02-09 | 2011-03-16 | Thomas Jefferson University | Diagnosis and treatment of cancers with microRNA located in or near cancer-associated chromosomal features |
| CN102399870A (en) * | 2006-11-28 | 2012-04-04 | 博奥生物有限公司 | Reagent for determining survival and prognosis of patients with esophagus cancer |
Non-Patent Citations (1)
| Title |
|---|
| Effect of Alcohol on miR-212 Expression in Intestinal Epithelial Cells and Its Potential Role in Alcoholic Liver Disease;Yueming Tang,et al;《Alcoholism: Clinical and Experimental Research》;20080229;第32卷(第2期);355–364 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103160509A (en) | 2013-06-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Economopoulou et al. | Liquid biopsy: an emerging prognostic and predictive tool in head and neck squamous cell carcinoma (HNSCC). Focus on circulating tumor cells (CTCs) | |
| Ding et al. | Perspectives of the application of liquid biopsy in colorectal cancer | |
| CN104152452B (en) | A kind of blood miRNA marker relevant to hepatocarcinoma and application thereof | |
| CN104164474A (en) | Fluorescent quantitative PCR method for detecting expression quantities of PCA3 gene and PSA gene in urine and diagnosis kit thereof | |
| Yin et al. | Serum/plasma microRNAs as biomarkers for HBV-related hepatocellular carcinoma in China | |
| Zhang et al. | Serum miR-483-5p as a potential biomarker to detect hepatocellular carcinoma | |
| CN104152567B (en) | MiRNA-199a is preparing the purposes in diagnostic kit | |
| CN105176983A (en) | Kit for detecting esophageal squamous carcinoma associated serum miRNAs genes | |
| Bijnsdorp et al. | The non-coding transcriptome of prostate cancer: implications for clinical practice | |
| CN103173450B (en) | Esophagus cancer postoperative early-stage recurrence and prognosis related miRNA marker and its application | |
| CN104694623A (en) | Plasma miRNA marker for diagnosis of lung cancer and application | |
| CN103173449B (en) | Esophagus cancer postoperative early-stage recurrence and prognosis related miRNA marker and its application | |
| El-Daly et al. | Circulating microRNAs as reliable tumor biomarkers: Opportunities and Challenges facing Clinical Application | |
| CN103074431B (en) | Special primer, kit and method for testing minRNA-128 in colorectal cancer serum | |
| CN106191055A (en) | A kind of non-small cell lung carcinoma marker, detectable and test kit | |
| CN105647923B (en) | Serum miRNA marker related to liver cancer prognosis and application of detection kit thereof | |
| CN103114092B (en) | MiRNA marker associated with post-esophageal-cancer-operation early recurrence and prognosis and applications thereof | |
| CN102925444A (en) | Serum micro ribonucleic acid (miRNA) biomarker of bladder cancer and detection method of expression quantity thereof | |
| Mengual et al. | Gene expression profiles in prostate cancer: identification of candidate non-invasive diagnostic markers | |
| CN103160509B (en) | miRNA marker relative to esophagus cancer postoperative early relapse and prognosis and application | |
| CN101988062A (en) | cervical cancer detection markers and detection method, kit and biochip thereof | |
| CN105087758A (en) | MiRNA detection kit for lung cancer prognostic prediction | |
| CN103911436A (en) | Serum/plasma miRNA marker for early diagnosis of noncardiac gastric carcinoma and applications thereof | |
| CN105219841A (en) | The detection kit of a kind of lung cancer differential expression microRNA and application thereof | |
| CN107326092A (en) | Applications and colorectal cancer detection kit of the related miRNA of colorectal cancer as biomarker |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20181203 Address after: 453000 Torch Garden, Xinfei Avenue, Xinxiang City, Henan Province, 5th Floor Co-patentee after: The First Affiliated Hospital of Xinxiang Medical University Patentee after: Henan Punoyi Biological Products Research Institute Co., Ltd. Address before: 453199 No. 88 Health Road, Weihui City, Xinxiang City, Henan Province Patentee before: The First Affiliated Hospital of Xinxiang Medical University |
|
| TR01 | Transfer of patent right |