CN107677825B - A kind of tumor diagnosis composition for diagnosis of cervical cancer and the purposes for being used to prepare diagnostic kit - Google Patents
A kind of tumor diagnosis composition for diagnosis of cervical cancer and the purposes for being used to prepare diagnostic kit Download PDFInfo
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- CN107677825B CN107677825B CN201710926283.6A CN201710926283A CN107677825B CN 107677825 B CN107677825 B CN 107677825B CN 201710926283 A CN201710926283 A CN 201710926283A CN 107677825 B CN107677825 B CN 107677825B
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Abstract
The invention discloses a kind of tumor diagnosis compositions for diagnosis of cervical cancer and the purposes for being used to prepare diagnostic kit.When serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) or N- phenylpropyl alcohol acyl-L-Glutamine diagnosis differentiation cervical cancer patient and healthy volunteer is used alone, area (AUC) is below 0.7 under ROC curve；AUC can be improved to 0.945 when triple combination distinguishes cervical cancer patient and healthy volunteer for diagnosing.One skilled in the art will appreciate that area is between 1.0 and 0.5 under ROC curve, in the case where AUC > 0.5, AUC illustrates that diagnosis effect is better closer to 1.AUC has lower accuracy in 0.5-0.7, and AUC has certain accuracy in 0.7-0.9, and AUC has high accuracy at 0.9 or more.Therefore, serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine can combine the diagnostic kit for being used to prepare diagnosing cervical.
Description
Technical field
The invention belongs to medical diagnosis on disease fields, are related to diagnosis marker, and in particular to a kind of for the swollen of diagnosis of cervical cancer
Tumor diagnosis composition and the purposes for being used to prepare diagnostic kit.
Background technique
Cervical carcinoma is one of most common genital tract malignant tumour of women, is in the first place of female reproductive system cancer, closely
Nian Lai, with the increase of the sexually transmitted diseases such as human papillomavirus, the disease incidence of cervical carcinoma increases year by year, and age of onset becomes
To rejuvenation.Cervical carcinoma early treatment prognosis bona, and advanced stage finds then poor prognosis.Therefore, the early discovery of cervical carcinoma, early diagnosis
Disconnected, early treatment is significant to the survival rate for improving cervical cancer patient.
In recent years, the report that morbidity and course of disease mechanism are studied with omics technology gradually increases, including genomics,
MicroRNA group, protein science, metabolism group etc..Wherein, metabolism group can mutually turn between tracing detection metabolin
Change and change with contents level, the biochemistry and physiological function change in these information and pathophysiological process connect can
Using as potential target and action site, and then determine relevant biomarker.With genomics and protein science etc. other
Omics technology compares, and metabolism group can show its advantage: 1. under metabolism group response gene and albumen level comprehensive function
Final result, and the faint variation of gene and albumen has " multiplier effect " in metabolism group；2. body small molecular compound
Composition it is relatively easy, it is easier to illustrate its biological function；3. the data analysis of metabolism group can pass through the number such as KEGG or HMDB
It is assisted according to library.
Noninvasiveization, high efficiency and hommization of diagnosis of cervical cancer may be implemented for diagnosing cervical for metabolic markers.
Summary of the invention
The purpose of the present invention is to provide a kind of tumor diagnosis composition for diagnosis of cervical cancer and it is used to prepare diagnosis
The purposes of kit, can quick diagnosis cervical carcinoma to pass through serum.
The present invention is achieved by following technical solution:
Lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine joint are used
In the purposes for the diagnosis composition for preparing diagnosing cervical.
Preferably, the lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L- paddy ammonia
Amide is serum hemolysis phosphatidyl choline (18:2), serum paraoxonase acyl inositol (20:4/0:0) and serum N-phenylpropyl alcohol acyl-L- paddy ammonia
Amide.
Lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine joint are used
In the purposes for the diagnostic kit for preparing diagnosing cervical.
Preferably, the lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L- paddy ammonia
Amide is serum hemolysis phosphatidyl choline (18:2), serum paraoxonase acyl inositol (20:4/0:0) and serum N-phenylpropyl alcohol acyl-L- paddy ammonia
Amide.
Advantages of the present invention:
Serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) or N- phenylpropyl alcohol acyl-L- paddy is used alone
When cervical cancer patient and healthy volunteer are distinguished in glutamine diagnosis, area (AUC) is below 0.7 under ROC curve；Triple combination uses
AUC can be improved to 0.945 when cervical cancer patient and healthy volunteer are distinguished in diagnosis.One skilled in the art will appreciate that ROC is bent
Area is between 1.0 and 0.5 under line, and in the case where AUC > 0.5, AUC illustrates that diagnosis effect is better closer to 1.AUC exists
There is lower accuracy when 0.5-0.7, AUC has certain accuracy in 0.7-0.9, and AUC has high accuracy at 0.9 or more.
Therefore, serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine can join
Close the diagnostic kit for being used to prepare diagnosing cervical.
Detailed description of the invention
Fig. 1 is that serum hemolysis phosphatidyl choline (18:2) is individually used for distinguishing the ROC of cervical cancer patient and healthy volunteer
Curve；
Fig. 2 is that serum paraoxonase acyl inositol (20:4/0:0) is individually used for distinguishing the ROC of cervical cancer patient and healthy volunteer
Curve；
Fig. 3 is that serum N-phenylpropyl alcohol acyl-L-Glutamine is individually used for distinguishing cervical cancer patient and the ROC of healthy volunteer is bent
Line；
Fig. 4 is serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L- glutamy
Amine combines the ROC curve for distinguishing cervical cancer patient and healthy volunteer.
Specific embodiment
It is further described technical solution of the present invention combined with specific embodiments below.
One, experimental material
Cervical cancer patient serum specimen is derived from the attached middle large hospital cervical carcinoma postoperative patients of Southeast China University.All patient's arts
It is preceding not receive the treatment such as radiotherapy, chemotherapy and anti-tumor drug, there is complete clinical and pathological data.Cervical carcinoma
Patient 95 (cervical carcinoma group), the age 31-62 years old, average age 53.3 years old.
Healthy volunteer's serum specimen 40 (Normal group), the age 32-65 years old, average age 54.5 years old.
Age composition no significant difference between cervical carcinoma group and Normal group.
Two, experimental method
1, serum sample pre-treatment
It takes 200 μ L serum in 1.5mL centrifuge tube, the 2- isopropylmalate acid solution internal standard of 50 μ L 1mg/mL, whirlpool is added
It revolves 20 seconds and mixes, the mixed solution (ratio 2.5: 1: 1) of 400 μ L methanol, chloroform and water is added, then in 70 DEG C of metal bath
Upper shaking 30min (1200rpm), 16000g × 5min are centrifuged (4 DEG C), take 500 μ L supernatants in 1.5mL centrifuge tube, are added 500
μ L distilled water is vortexed and mixes, and then 16000g × 5min is centrifuged (4 DEG C), takes 500 μ L supernatants in 1.5mL centrifuge tube, in room temperature
Lower to be dried up with nitrogen evaporator, the residue obtained methoxamine pyridine solution with 80 μ L dissolves, and 60 μ L are added in oximate 8h under the conditions of 50 DEG C
N- methyl-N- trimethyl silicon substrate trifluoroacetamide, under the conditions of 70 DEG C derivatization 2h to get.
2, GC-MS is analyzed
The 2 μ L of sample of above-mentioned derivatization is taken to carry out GC-MS analysis.
Liquid phase chromatogram condition is as follows: injector temperature: 270 DEG C；Sample volume: 2.0 μ L；Splitless injecting samples, carrier gas: high-pure helium
(99.999%)；Flow velocity: 1.0mL/min；Interface temperature: 260 DEG C；Chromatographic column: DB-5MS capillary column, chromatography column and programmed temperature
It is detected, 80 DEG C of constant temperature 2min, 80 DEG C -300 DEG C (5 DEG C/min) constant temperature 6min.
Mass Spectrometry Conditions are as follows: ion source temperature: 230 DEG C；Level four bars temperature: 150 DEG C, solvent delay: 5min；Electron collision
Ionization voltage: 70eV, mass spectrum full scan range (m/z): 30-600, using full scan mode.
Respectively with lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) or N- phenylpropyl alcohol acyl-L-Glutamine
Chromatographic peak area divided by the peak area of internal reference 2- isopropylmolic acid, gained ratio is respectively as hemolytic phosphatidyl in each sample
Choline (18:2), phosphatidylinositols (20:4/0:0) or N- phenylpropyl alcohol acyl-L-Glutamine relative amount.
3, statistical procedures
It is analyzed using 20.0 software of SPSS, is indicated with mean value ± deviation, comparison among groups are examined using t.Evaluation is every
Index application value draws Receiver Operating Characteristics (ROC) curve, and area (AUC) under calculated curve；It is poor with P < 0.05
It is different statistically significant.Each single index and Joint Index are evaluated to the diagnostic value of cervical carcinoma using ROC curve.
Three, experimental result
1, between two groups Tumor Marker Levels comparison
The relative amount of lysophosphatidyl choline (18:2) is significantly lower than Normal group, cervical carcinoma in cervical carcinoma group serum
Phosphatidylinositols (20:4/0:0), N- phenylpropyl alcohol acyl-L-Glutamine relative amount are obviously higher than normal control in group serum
Group, difference are statistically significant (t value is respectively 1.733,1.479 and 2.314, P < 0.01).Comparison result is as shown in table 1.
The comparison (mean value ± deviation) of Tumor Marker Levels between 1 two groups of table
2, tumor-marker analyte detection cervical carcinoma ROC curve is analyzed
Serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) or N- phenylpropyl alcohol acyl-L- paddy is used alone
When cervical cancer patient and healthy volunteer are distinguished in glutamine diagnosis, area (AUC) is below 0.7 under ROC curve；Triple combination uses
AUC can be improved to 0.945 when cervical cancer patient and healthy volunteer are distinguished in diagnosis.It can be seen that serum hemolysis phosphatidyl
Choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine triple combination have for diagnosing cervical
There is higher clinical value.The ROC curve analysis of three indexs combines dualistic logistic regression to operate.
ROC curve analyzes result as shown in table 2 and Fig. 1-4.
2 three serum protein moteblites of table are individually and Combining diagnosis value compares
One skilled in the art will appreciate that area is between 1.0 and 0.5 under ROC curve, and in the case where AUC > 0.5, AUC
Closer to 1, illustrate that diagnosis effect is better.AUC has lower accuracy in 0.5-0.7, and AUC is fixed in 0.7-0.9 Shi Youyi
True property, AUC have high accuracy at 0.9 or more.Therefore, serum hemolysis phosphatidyl choline (18:2), phosphatidylinositols (20:
4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine can combine the diagnostic kit for being used to prepare diagnosing cervical.
Claims (2)
- It is used for 1. lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine are combined Prepare the purposes of the diagnosis composition of diagnosing cervical, the lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0: 0) and N- phenylpropyl alcohol acyl-L-Glutamine be serum hemolysis phosphatidyl choline (18:2), serum paraoxonase acyl inositol (20:4/0:0) and Serum N-phenylpropyl alcohol acyl-L-Glutamine.
- It is used for 2. lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0:0) and N- phenylpropyl alcohol acyl-L-Glutamine are combined Prepare the purposes of the diagnostic kit of diagnosing cervical, the lysophosphatidyl choline (18:2), phosphatidylinositols (20:4/0: 0) and N- phenylpropyl alcohol acyl-L-Glutamine be serum hemolysis phosphatidyl choline (18:2), serum paraoxonase acyl inositol (20:4/0:0) and Serum N-phenylpropyl alcohol acyl-L-Glutamine.
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| WO2016041013A1 (en) * | 2014-09-16 | 2016-03-24 | Baker Idi Heart And Diabetes Institute Holdings Limited | Glycerolipids and uses therefor |
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| WO2001036977A2 (en) * | 1999-11-16 | 2001-05-25 | Matritech, Inc. | Identification of disease markers involving mass-based-separation |
| CN102884435A (en) * | 2009-11-27 | 2013-01-16 | 贝克Idi心脏和糖尿病研究院控股有限公司 | Lipid biomarkers for stable and unstable heart disease |
| WO2011072130A1 (en) * | 2009-12-10 | 2011-06-16 | Purdue Research Foundation | Methods for diagnosing or monitoring for recurrence of prostate cancer |
| WO2016041013A1 (en) * | 2014-09-16 | 2016-03-24 | Baker Idi Heart And Diabetes Institute Holdings Limited | Glycerolipids and uses therefor |
| CN105445408A (en) * | 2016-01-25 | 2016-03-30 | 齐炼文 | Metabolite marker for diagnosing and distinguishing coronary atherosclerosis and stable angina pectoris |
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