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Abnormal Expression of DNA Double-Strand Breaks Related Genes, ATM and GammaH2AX, in Thyroid Carcinoma
Jin-Lin Hu1, Si-Si Hu2, Xiu-Xiu Hou3
1Department of Pathology, Zhejiang Province Cancer Hospital, Hangzhou 310022, China.
Abstract:
ATM and γH2AX play a vital role in the detection of DNA double-strand breaks (DSB) and DNA damage response (DDR). This study aims to investigate ATM and γH2AX expression in thyroid cancer and discuss possible relationship between thyroid function tests and DNA damage. The expression of ATM and γH2AX was detected by immunohistochemistry in 30 cases of benign nodular goiter, 110 cases of well differentiated thyroid cancer, 22 cases of poorly differentiated thyroid cancer, and 21 cases of anaplastic thyroid cancer. Clinicopathological features, including differentiation stages, distant metastasis, lymph node metastasis, T classification, TNM stage, and tests of thyroid functions (TPOAb, Tg Ab, T3, FT3, T4, FT4, TSH, and Tg), were reviewed and their associations with γH2AX and ATM were analyzed. γH2AX and ATM expressed higher in thyroid cancer tissues than in benign nodular goiter and normal adjacent tissues. γH2AX was correlated with ATM in thyroid cancer. Both γH2AX and ATM expression were associated with FT3. γH2AX was also associated with T classification, TNM stage, FT4, TSH, and differentiation status. Therefore both of ATM and γH2AX seem to correlate with thyroid hormones and γH2AX plays a role in the differentiation status of thyroid cancer.
Insights
ATM and γH2AX, key DNA damage response proteins, are elevated in thyroid cancer. Their expression correlates with thyroid hormone levels and cancer progression, suggesting a role in thyroid cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- ATM (Ataxia-Telangiectasia Mutated) and γH2AX are critical in detecting DNA double-strand breaks (DSB) and initiating the DNA damage response (DDR).
- Understanding their role in thyroid cancer pathogenesis is crucial for potential diagnostic and therapeutic advancements.
Purpose of the Study:
- To investigate the expression levels of ATM and γH2AX in various thyroid cancer types and benign thyroid tissues.
- To explore the association between ATM and γH2AX expression and clinicopathological features, including thyroid function tests.
Main Methods:
- Immunohistochemistry was employed to detect ATM and γH2AX expression in 30 benign nodular goiters, 110 well-differentiated thyroid cancers, 22 poorly differentiated thyroid cancers, and 21 anaplastic thyroid cancers.
- Clinicopathological data and thyroid function test results (TPOAb, Tg Ab, T3, FT3, T4, FT4, TSH, Tg) were analyzed for correlations with ATM and γH2AX expression.
Main Results:
- ATM and γH2AX expression were significantly higher in thyroid cancer tissues compared to benign nodular goiter and normal adjacent tissues.
- γH2AX expression was positively correlated with ATM expression in thyroid cancer.
- Both ATM and γH2AX expression levels showed associations with specific thyroid function tests, notably FT3, FT4, and TSH. γH2AX also correlated with T classification, TNM stage, and differentiation status.
Conclusions:
- ATM and γH2AX are upregulated in thyroid cancer, indicating their involvement in DNA damage and response pathways within these tumors.
- The correlation of ATM and γH2AX with thyroid hormones (FT3, FT4, TSH) suggests a potential interplay between thyroid function and DNA damage mechanisms in thyroid cancer.
- γH2AX expression is linked to the differentiation status of thyroid cancer, highlighting its potential role in tumor progression and aggressiveness.
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