Abstract
BackgroundDiagnosis of breast cancer is more complicated due to lack of minimal invasive biomarker with sufficient precision. DNA methylation is a promising marker for cancer diagnosis. In this study, authors evaluated methylation patterns for PTEN and SMAD4 in blood samples using EpiTect Methyl II QPCR assay quantitative PCR technology. ResultsMethylation status for PTEN and SMAD4 were statistically significant as breast cancer patients reported hypermethylation compared to benign and control groups (77.1 ± 17.9 vs. 24.9 ± 4.5 and 15.1 ± 1.4 and 70.1 ± 14.4 vs. 28.2 ± 0.61 and 29.5 ± 3.6, respectively). ROC curve analysis revealed that both PTEN (AUC = 0.992) and SMAD4 (AUC = 0.853) had good discriminative power for differentiating BC from all non-cancer individuals (benign and healthy combined) compared to routine tumor markers CEA (AUC = 0.538) and CA15.3 (AUC = 0.686). High PTEN methylation degree was associated with late stages (84.2 ± 17.4), positive lymph node (84.2 ± 18.5), positive ER (81.3 ± 19.7), positive PgR (79.5 ± 19.1), and positive HER2 (80.7 ± 19.0) vs. 67.4 ± 13.8, 70.6 ± 14.8, 72.8 ± 14.9, 72.5 ± 14.7, and 70.2 ± 13.5 in early stages, negative lymph node, negative ER, negative PgR, and negative HER2, respectively. Similar results were obtained regarding SMAD4 methylation. Sensitivity, specificity, positive and negative predictive values, and accuracy for methylated PTEN were 100%, 95%, 99.1%, 100%, and 95%, respectively when differentiated BC from all-non cancer controls. Interestingly, PTEN could distinguish early BC stages with good sensitivity 84.4%, 51.4%, 69.1%, 72%, and 70%, respectively. ConclusionMethylation status of PTEN and SMAD4 is a promising blood marker for early detection of breast cancer. Future studies are needed for their role as prognostic markers.
Highlights
Diagnosis of breast cancer is more complicated due to lack of minimal invasive biomarker with sufficient precision
Aberrant promoter methylation of numerous tumor suppressor genes was obtained in Breast cancer (BC) initiator lesions, representing that DNA methylation is an early event in breast carcinogenesis [10]
Despite CEA (AUC = 0.538) and CA15.3 (AUC = 0.686), Receiver operating characteristic (ROC) curve analysis revealed that both Phosphatase and tensin homolog (PTEN) (AUC = 0.992) and SMAD4 (AUC = 0.853) had extremely discriminative power for good differentiating BC from all non-cancer individuals
Summary
Diagnosis of breast cancer is more complicated due to lack of minimal invasive biomarker with sufficient precision. DNA methylation is a promising marker for cancer diagnosis. Breast cancer (BC) is the most widely neoplasm in women [1] that progresses silently, leading to neighboring metastasis and poor prognosis. Epigenetic mutations, involved DNA methylation, were responsible for the control of gene expression by regulating gene transcription [8]. Most DNA methylation is catalyze by DNA methyltransferases and exhibits essential physiological role in numerous key functions of cells [9]. Aberrant promoter methylation of numerous tumor suppressor genes was obtained in BC initiator lesions, representing that DNA methylation is an early event in breast carcinogenesis [10]
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