A novel methylation site of SFRP1 Gene Promoter in colorectal cancer: Potential utility as biomarker for prognosis and immunotherapy

Abstract

Abstract The methylation level of the SFRP1 gene promoter is closely related to colorectal cancer. 205 stool samples were enrolled and were divided into positive and negative groups in the study. MassArray was used to screen the level of methylation on the SFRP1 gene promoter in the two groups. A random forest model was established to analyze and screen methylation sites of characteristic expression. A further 60 fecal samples were collected and divided into positive and negative groups to verify the specificity and sensitivity of the characteristic methylation sites by RT-PCR. TCGA database was used to analyze the relationship between tumor immunity and methylation sites in CRC patients. 12 differentially expressed MassArray detected methylation sites on SFRP1 promoter in colorectal cancer or adenoma stool specimens compared to normal. Random forest regression models built using the R package randomForest analysis (OOB error rate is 39.29%) located in the OOB error fastest changing area and have a good performance (accuracy: 0.757, sensitivity: 0.857, specificity: 0.696). The cg15839448, cg17816908 and cg14548509 showed better on specificity and sensitivity. Further, RT-PCR analysis showed that SFRP1_CpG_16.17.18 (cg17816908) performed best between the three CpG sites. The AUC of the ROC curve is 0.791, which was higher than the other two CpG sites. And cg17816908 is negatively correlated with prognosis and immune checkpoints with immunotherapy sensitivity in CRC patients. Our study demonstrated that SFRP1_CpG_16.17.18 (cg17816908) has a good clinical performance as a prognosis marker of colorectal cancer, and may provide a reference to immunotherapy in the clinic.