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Click [Medical Formula] Follow us, everyone! Today I will share with you a new article on prostate cancer published in March 2021 (IF=5.
1, American Journal of Cancer Research).
Literature name: Genome-wide DNA methylation profiling of leukocytes identifies CpG methylation signatures of aggressiveprostate cancer PCa is the most common cancer among men in the United States and the second leading cause of cancer deaths.
The onset is asymptomatic at first, until aggravation or metastasis occurs.
In order to find biomarkers and risk stratification that are independent of clinical features to diagnose diseases and reduce overtreatment, this paper conducts leukocyte whole-genome DNA methylation analysis on 287 PCa (GS=6, GS≥8), by constructing 5 times Cross-validation of the random forest model, screening a methylation model containing 97 DMPs (AUC=0.
920, prediction accuracy=0.
847).
Whole Genome Methylation Analysis Research subjects 287 prostate cancer PCa patients (divided into two groups based on their GS scores) performed a 450k chip whole-genome methylation analysis on their white blood cells, and compared the differences in methylation between the two groups.
The results of the study found that the average methylation levels of the two groups in the TSS200 and Exon1 regions were statistically different.
Subsequently, 10264 DMPs (6876 hyer-, 3389 hypo-) were obtained through differential analysis.
It was found that in TSS200, Exon 1, 5'UTR, TSS1500, genebody there are more hypermethylated genes than hypomethylated genes, while 3'UTR, There was no statistical difference between the two in IGR.
The level of white blood cell methylation can estimate the proportion of white blood cell subpopulations, and it is found that the proportions of white blood cell subpopulations in the two groups are similar, indicating that the difference in white blood cell methylation is unlikely to be caused by differences in immune cells.
Constructing a methylation model By setting a threshold FDR<0.
01, screening out 1,459 CpG, and constructing a 5-fold cross-validation random forest model, obtaining an AUC of 0.
836 and a prediction accuracy of 0.
757.
Then sorted according to the importance of probes, and screened out highly correlated The model built by the probe, the prediction accuracy is increased by 80%.
The final prediction model includes 97 highly correlated DMPs, with an AUC of 0.
925 and a prediction accuracy of 0.
847.
The multidimensional scale MDS indicates that the model has a high degree of clustering ability for patients.
The heat map shows the methylation level of these 97 DMPs, which shows that the model has a high diagnostic ability for patients.
Comparison of the methylation level of PCa patients with normal people The methylation data of white blood cell PCa patients measured before and compared with 172 normal people in GSE85210.
The results showed that the overall methylation level of PCa patients was lower than that of normal people, but the TSS200 and Exon1 regions were higher than normal people.
In summary, this topic is very novel and the patient data is huge.
287 patients were included for 450k genome-wide methylation analysis, and a random forest model was established to obtain a methylation model with high prediction accuracy.
Whether in terms of the number of objects or the machine method, the persuasive power is very strong, which is very suitable for us to imitate and learn by reference.
Regarding the shortcomings, the author of the article also proposed a few: This article only includes patients with GS=6 and GS≥8, because they have significantly different clinical phenotypes, and they can diagnose the disease by establishing a methylation model.
However, patients with GS=7 have a moderate risk of progression, and the outcome is uneven and difficult to predict.
In the future, more in-depth studies can be conducted on this type of patients.
The END call for papers "Medical Formula" is now officially open to fans! The content must be originally published and related to scientific research.
Once adopted, a generous reward (300-2000 yuan) will be given.
Please stamp for details.
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