CN118050514A - Application of SAM in early screening and diagnosing colorectal cancer - Google Patents
Application of SAM in early screening and diagnosing colorectal cancer Download PDFInfo
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- CN118050514A CN118050514A CN202410294612.XA CN202410294612A CN118050514A CN 118050514 A CN118050514 A CN 118050514A CN 202410294612 A CN202410294612 A CN 202410294612A CN 118050514 A CN118050514 A CN 118050514A
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- 238000002965 ELISA Methods 0.000 claims abstract description 13
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- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 29
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- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The application relates to the technical field of biomedicine, in particular to application of SAM as a biomarker in preparing early-stage screening and colorectal cancer diagnosis products. SAM concentrations in colorectal cancer patients were found to be significantly higher in plasma than in normal control populations. The present study, by detecting peripheral blood SAM levels, found SAM to be a diagnostic biomarker for CRC. The ELISA method can detect in serum, is convenient and accurate, has low cost, and is an experimental diagnosis method suitable for clinical development.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to application of SAM in early screening and diagnosing colorectal cancer.
Background
Colorectal cancer (CRC) is a malignant tumor of the global high-frequency digestive system, currently considered the fourth most fatal cancer in the world. The incidence of CRC in various regions and countries worldwide has increased at least doubled during the last 30 years. Diagnosis and treatment of CRC are very severe.
The current screening means for colorectal cancer are relatively limited, mainly based on fecal occult blood test, colonoscopy and serum and plasma markers, and the specificity and sensitivity of the former two are not high, and the possibility of early diagnosis is not high. The fecal occult blood test is highly likely to be affected by food or physiological factors. Colonoscopy, however, is an invasive examination, and considering whether patients with colorectal cancer are older and resistant to the intensity of such examination, requires careful pre-operative evaluation, and also involves complications of the examination such as gastrointestinal bleeding, perforation of the digestive tract, etc. Currently, known serum tumor markers are not highly specific and often suffer from a large number of factors, such as rheumatic immune diseases, bacterial viral infections, etc., and are therefore not fully suitable for diagnosis and early diagnosis of colorectal cancer. There is also an increasing number of plasma secreted proteins and non-coding RNAs coming into the general line of sight and the content of research is becoming more and more intensive. Whether invasive or non-invasive examination tests, there is a need for indicators that have both specificity and sensitivity to aid in the diagnosis of colorectal cancer, and there is a need for continued exploration in the future.
The high mortality rate and the complexity of the mechanism of colorectal cancer indicate the necessity of diagnosis, and the abnormal methylation performance of colorectal cancer brings new opportunities for diagnosis. The diagnosis is generally confirmed by gold standard of pathology, the possibility of late stage of postoperative pathology stage is not small, so that accurate judgment can not be carried out only according to TNM stage, because patients with similar tissue pathology results can have different conditions due to genetic and epigenetic differences, the follow-up diagnosis and the estimated survival rate are related, and the diagnosis of CRC is more critical for disease prevention, treatment and even prognosis. In summary, early diagnosis and treatment of CRC is particularly critical, reducing mortality and improving prognosis are important.
Currently, carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 199), carbohydrate antigen 242 (CA 242), erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), and the like are not clear as diagnostic indicators of colorectal cancer direct targeting among serological tumor markers. Based on the abnormal methylation of colorectal cancer, a very large number of genes are considered as potential tumor markers, such as some of the genes already present: SFRP1/2, BMP3, SEPT9, etc. Meanwhile, the sensitivity of the existing methylation detection kit is respectively 48% -90%, and the specificity is 73% -97%.
In summary, methylation detection is still imperfect, different indexes have large differences, and an aspect to be improved needs to be related to methylation stability to determine methylation level, so as to achieve the effect of clear diagnosis.
Disclosure of Invention
The invention aims to solve the technical problems that CRC methylation detection is imperfect and different indexes have large difference in the prior art.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
Use of SAM as biomarker in the preparation of early screening and diagnosis colorectal cancer products.
Preferably, the product is a detection kit.
Preferably, the product is monitored using an enzyme-linked immunosorbent assay.
Preferably, the sample detected by the product is peripheral blood of a person to be detected.
The SAM provided by the application is used as a biomarker in the preparation of early screening and diagnosing colorectal cancer products, wherein the level of S-adenosylmethionine (SAM) in serum of colorectal cancer patients is based on the fact that SAM carries methyl transfer in epigenetic modification, and DNA, RNA or protein is taken as a methyl substrate, so that the SAM is superior to a gene with increased abnormal methylation in the aspect of measuring abnormal methylation, and secondly, the SAM can be used as a diagnosis biomarker of CRC by detecting the level of SAM in peripheral blood. The ELISA method can detect in serum, is convenient and accurate, has low cost, and is an experimental diagnosis method suitable for clinical development.
Drawings
FIG. 1 is a comparison of SAM levels in plasma of CRC patients and normal control populations by ELISA according to an embodiment of the present application;
FIG. 2 is a ROC curve (local data) of SAM diagnosis CRC according to an embodiment of the present application, where ROC: a subject work profile (Receiver Operating Characteristic curve); AUC (Area Under the Curve): area under ROC curve; 95% CI: a 95% confidence interval (Confidence Interval);
FIG. 3 is a ROC curve (local data) of CEA diagnostic CRC in an embodiment of the application;
FIG. 4 is a ROC curve (local data) of a CA19-9 diagnostic CRC in accordance with an embodiment of the application;
FIG. 5 is a ROC curve (local data) of CEA in combination with CA19-9 diagnostic CRC in one embodiment of the application;
FIG. 6 is a ROC curve of CEA diagnostic CRC in the TCGA database;
FIG. 7 is a ROC curve of CEA diagnostic CRC in the TCGA database;
FIG. 8 is a ROC curve of CEA-combined CA19-9 diagnostic CRC in the TCGA database.
Detailed Description
The present invention will be described in further detail with reference to specific examples.
Use of SAM as biomarker in the preparation of a product for early screening and diagnosis of colorectal cancer, in one embodiment the product is a detection kit, the product being detected using an enzyme-linked immunosorbent assay.
The detected sample is peripheral blood of a person to be detected.
The foregoing is described in conjunction with specific embodiments below:
All serum samples in the application were from CRC patients and normal physical examination populations of affiliated hospitals at university of Nantong. In this example, 42 CRC serum samples and 45 normal physical examination population serum samples were tested. All patients and people did not receive chemotherapy or radiation prior to blood collection. The study of this example was approved by the university of south-pass ethics committee and informed consent was provided by the patient or its authorizer.
The enzyme-linked immunosorbent assay (ELISA) kit used in this example was manufactured by Shanghai Saisesen Biotech Co. This example performed serum sample collection from 42 patients and 45 normal physical examination populations in the affiliated hospital of university of south China. No radiotherapy, chemotherapy, immunotherapy or other treatment was performed prior to blood collection. Ethical approval was approved by the human research ethics committee of affiliated hospitals at university of south tongtong (Jiangsu China).
Example 1: ELISA detects comparison of SAM levels in plasma of patients and normal control group:
referring to FIG. 1, the present application detects the content of S-adenosylmethionine (SAM) in blood plasma by enzyme-linked immunosorbent assay (ELISA) using mobile phone clinical data and blood samples.
The results are shown in figure 1, where SAM concentration in the plasma of colorectal cancer patients is significantly higher than in normal control population.
SAM acts as a direct donor of methyl groups and is active in one-carbon metabolism, especially in abnormally methylated CRC, so we detected SAM levels in plasma of CRC patients, and ELISA detection found that SAM levels in plasma of 42 CRC patients were significantly higher than in 45 normal control populations, P <0.0001, as shown in figure 1.
Example 2: subject working curve comparison:
Based on the relevant content of example 1, the concentrations of SAM in serum of CRC patient and normal control population were pooled into a subject working curve (ROC), as shown in fig. 2, the area under ROC curve (AUC) of sam=0.956, sensitivity 88.1% and specificity 97.8%. SAM as biomarker AUC greater than 0.9, demonstrated excellent diagnostic value.
In contrast to the existing carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA 199), the AUC of S-adenosylmethionine (SAM) was significantly higher than that of both, and referring to FIGS. 3-5, it can be seen that no SAM was effective for either CEA or CA199 alone or in combination.
Specifically, when CRC was diagnosed for CEA alone, the sensitivity was 91.8% and the specificity was 26.7%. The sensitivity was 75.5% and the specificity was 57.8% when CA19-9 was diagnosed alone. When CEA was diagnosed in combination with CA19-9, the sensitivity was 98% and the specificity was 37.8%. The diagnostic performance is significantly inferior to that of SAM. It should be noted that indexes such as sensitivity and specificity of CEA and CA19-9 are obtained only for data of 42 CRC patients and 45 normal control groups in the invention.
To further confirm the conclusion of this patent, we also used public database data such as TCGA to perform cross-validation, as shown in fig. 6-8, in TCGA database, the indexes of CEA and CA199 diagnose ROC curves of CRC, and AUC values are low, so that the diagnosing effect is poor. The database results further demonstrate that SAM is significantly better than CEA and CA19-9 in CRC diagnosis.
In summary, SAM is found to be useful as a diagnostic biomarker for CRC by detecting SAM levels in peripheral blood. And the ELISA method can be used for detecting in serum, is convenient and accurate, has low cost, and is an experimental diagnosis method suitable for clinical development.
Claims (4)
- Use of sam as biomarker for the preparation of a product for early screening and diagnosis of colorectal cancer.
- 2. Use of SAM according to claim 1 as biomarker for the preparation of early screening and diagnosis colorectal cancer products, characterized in that: the product is a detection kit.
- 3. Use of SAM according to claim 1 as biomarker for the preparation of early screening and diagnosis colorectal cancer products, characterized in that: the product was monitored using enzyme-linked immunosorbent assay.
- 4. Use of SAM according to claim 1 as biomarker for the preparation of early screening and diagnosis colorectal cancer products, characterized in that: the sample detected by the product is peripheral blood of a person to be detected.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410294612.XA CN118050514A (en) | 2024-03-15 | 2024-03-15 | Application of SAM in early screening and diagnosing colorectal cancer |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410294612.XA CN118050514A (en) | 2024-03-15 | 2024-03-15 | Application of SAM in early screening and diagnosing colorectal cancer |
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| CN118050514A true CN118050514A (en) | 2024-05-17 |
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| CN202410294612.XA Pending CN118050514A (en) | 2024-03-15 | 2024-03-15 | Application of SAM in early screening and diagnosing colorectal cancer |
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- 2024-03-15 CN CN202410294612.XA patent/CN118050514A/en active Pending
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