Abnormal Expression of DNA Double-Strand Breaks Related Genes, ATM and GammaH2AX, in Thyroid Carcinoma

Hu, Jinyu; Hu, Sunli; Hou, Xiuxiu; Zhu, Xin; Cao, Jun; Jiang, Liehao; Ge, Minghua

doi:10.1155/2015/136810

Cited by 13 publications

(11 citation statements)

References 34 publications

(39 reference statements)

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“…Increased γH2AFX expression may result in increased radiosensitivity ( 28 ). Multiple studies have revealed that γH2AFX expression is increased in certain types of cancer and their premalignant lesions ( 8 , 22 , 29 , 30 ), which supports the results of the present study. Overexpression of γH2AFX may represent an independent prognostic indicator of a poor overall patient survival rate ( 31 , 32 ).…”

Section: Discussionsupporting

confidence: 92%

“…Tumorigenic events that occur early in the progression of major types of human cancer activate ATM-regulated cell cycle checkpoints and thereby an inducible barrier that inhibits tumor progression and genetic instability ( 7 , 24 ). A previous study has demonstrated that ATM expression was increased in certain types of cancer tissue compared with that in benign tumorous lesions and normal tissues ( 22 ). Other previous studies have suggested that ATM potentially represents a promising indicator for hyperplasia and cancer, and may serve as a useful marker for identifying patients with poor prognosis ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…Positive staining intensity was defined as 0, 1, 2, and 3 for no staining, light yellow, yellow brown, and brown, respectively. The scoring method used for ATM and γH2AFX was referred to by Hu et al ( 22 ). The positive cell percentages of 0, 1–25, 26–50, 51–75, and >75 were defined as 0, 1, 2, 3, and 4, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Expression of DNA doublestrand repair proteins in oral leukoplakia and the risk of malignant transformation

et al. 2018

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The present study assessed the expression of the DNA doublestrand repair (DDR) proteins ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2) and γH2A histone family member X (γH2AFX) in oral leukoplakia (OL) and evaluated their clinical significance and usefulness as biomarkers for predicting OL transformation. Retrospectively, ATM, CHEK2 and γH2AFX protein levels were evaluated using immunohistochemical analysis in 61 OL, 33 oral squamous cell carcinoma (OSCC) and 15 normal oral mucosa tissues. OL tissues were classified into two groups according to the epithelial dysplasia pathology: The low risk dysplasia group (n=41) and the high-risk dysplasia group (n=20). The results of the present study revealed that the expression of ATM and γH2AFX in OSCC was significantly increased compared with that in OL with low-risk dysplasia and normal oral mucosa tissues. There was no statistically significant difference in CHEK2 expression among the groups. ATM expression was correlated with that of γH2AFX in OSCC tissue. The prognostic values of the DDR proteins and their correlation with clinical and pathological parameters were evaluated further in 99 OL patients with low risk dysplasia. Multivariate analysis revealed that increased expression of ATM and γH2AFX was significantly associated with an increased risk of malignant transformation. Immunohistochemical analysis of ATM and γH2AFX protein expression provided useful prognostic information on the carcinogenesis of OL. Increased ATM and γH2AFX expression may indicate a poor prognosis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Expression of DNA doublestrand repair proteins in oral leukoplakia and the risk of malignant transformation

et al. 2018

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“…In another study, gH2AX was found to play a role in the differentiation status of thyroid cancer. 69…”

Section: Resultsmentioning

confidence: 99%

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Palla¹,

Karaolanis

Katafigiotis

et al. 2017

Tumour Biol.

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Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to doublestrand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers. The prognostic value of gamma-H2AX is indicated in certain cancer types, such as breast or endometrial cancer, but further investigation is needed to establish gamma-H2AX as a prognostic marker. This review outlines the role of gamma-H2AX in cell cycle, and its formation as a result of DNA damage. We investigate the role of gamma-H2AX formation in several cancer types and its correlation with other prognostic factors, and we try to find out whether it fulfills the requirements for its establishment as a classical cancer prognostic factor.

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“…Ataxia-telangiectasia mutated (ATM) is newly discovered gene that can initiate the repair of DNA double-strand breaks, and the expression level of ATM is closely correlated with the repair of damaged cells and the regulation of apoptosis cycle ( 5 ). Studies have shown that ( 6 – 8 ) abnormal expression of ATM plays pivotal roles in the occurrence of lung cancer, breast cancer, thyroid cancer and other types of cancers by regulating gene expression and angiogenesis. In addition, abnormal cell apoptosis is also a cause of the development and progression of tumor.…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer

Xiong

Zhang

2017

Oncol Lett

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The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= −0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (P<0.05). The results showed that ATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.

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Abnormal Expression of DNA Double-Strand Breaks Related Genes, ATM and GammaH2AX, in Thyroid Carcinoma

Cited by 13 publications

References 34 publications

Expression of DNA doublestrand repair proteins in oral leukoplakia and the risk of malignant transformation

Expression of DNA doublestrand repair proteins in oral leukoplakia and the risk of malignant transformation

gamma-H2AX: Can it be established as a classical cancer prognostic factor?

Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer

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