Evaluation of TAGLN as a diagnostic marker in breast cancer
Embargo Lift Date: 2019-03-03
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Silecing of tumor suppressor genes via CpG hypermethylation in promoter regions is one of the frequent events occurring in different types of cancers. These genes have the potential as a diagnostic or a prognostic biomarker. Liquid biopsy is a relatively less invasive technique that is used for early diagnosis, therapy response prediction, minimal residual disease detection and real-time monitoring of tumor progression. In this study, a 402 bp region (-286 bp to -80 bp for Section 1, -102 bp to +115 bp for Section 2) located in TAGLN promoter containing 22 CpGs was analyzed in breast cancer patients and healthy donors to evaluate the biomarker potential of TAGLN promoter methylation levels in breast cancer. TAGLN promoter region was significantly hypermethylated in breast cancer patients (77.3%) compared to healthy donors (68.2%). Among differentially methylated CpGs, 6 out of 22 were hypermethylated and one was hypomethylated in breast cancer patients. We also analyzed the relationship between TAGLN promoter methylation levels and the patient's clinicopathological parameters. Analyses revealed that TAGLN promoter is highly methylated in breast cancer patients over 50 years of age compared to the healthy donors in the same age group. TAGLN promoter methylation did not differ as related to various clinicopathological parameters of breast cancer patients. TAGLN promoter methylation levels diagnosed breast cancer patients with 74.45% specificity and 57.58% sensitivity. Additionally, independent of the age group breast cancer patients (131.6 ng) exhibited higher levels of total cfDNA compared to healthy donors (56.4 ng). Pre- and postmenopausal breast cancer patients possessed higher total cfDNA levels compared to pre- and postmenopausal healthy donors. Total cfDNA levels did not differ in various clinicopathological parameters of breast cancer patients; however, total cfDNA levels diagnosed breast cancer patients with 73.33% specificity and 56.72% sensitivity. In summary, breast cancer patient sera can be used to identify the tumor profile, and TAGLN promoter hypermethylation and total cfDNA levels could serve as a diagnostic biomarker in breast cancer.
Cell-Free Circulating DNA