Evaluation of TAGLN as a diagnostic marker in breast cancer
Author
Köseer, Ayşe Sedef
Advisor
Yuluğ, Işık
Date
2018-09Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
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.
Keywords
TransgelinTAGLN
SM22 Alpha
Breast Cancer
DNA Methylation
Hypermethylation
Biomarker
Diagnosis
Cell-Free Circulating DNA
cfDNA