Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the
SRCIN1 gene in breast cancer patients. We assessed
SRCIN1-related roles and pathways for their biomarker potential. To
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Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the
SRCIN1 gene in breast cancer patients. We assessed
SRCIN1-related roles and pathways for their biomarker potential. To verify the methylation status, quantitative methylation-specific PCR (qMSP) was performed on genomic DNA and circulating cell-free DNA samples, and mRNA expression analysis was performed using RT‒qPCR. The results were validated in a Western population; for this analysis, the samples included plasma samples from breast cancer patients from the USA and from The Cancer Genome Atlas (TCGA) cohort. To study the
SRCIN1 pathway, we conducted cell viability assays, gene manipulation and RNA sequencing.
SRCIN1 hypermethylation was identified in 61.8% of breast cancer tissues from Taiwanese patients, exhibiting specificity to this malignancy. Furthermore, its presence correlated significantly with unfavorable 5-year overall survival outcomes. The levels of methylated
SRCIN1 in the blood of patients from Taiwan and the USA correlated with the stage of breast cancer. The proportion of patients with high methylation levels increased from 0% in healthy individuals to 63.6% in Stage 0, 80% in Stage I and 82.6% in Stage II, with a sensitivity of 78.5%, an accuracy of 90.3% and a specificity of 100%.
SRCIN1 hypermethylation was significantly correlated with increased
SRCIN1 mRNA expression (
p < 0.001). Knockdown of SRCIN1 decreased the viability of breast cancer cells.
SRCIN1 silencing resulted in the downregulation of ESR1, BCL2 and various cyclin protein expressions.
SRCIN1 hypermethylation in the blood may serve as a noninvasive biomarker, facilitating early detection and prognosis evaluation, and
SRCIN1-targeted therapies could be used in combination regimens for breast cancer patients.
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