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Overexpression of RAD50 is the Marker of Poor Prognosis and Drug Resistance in Breast Cancer Patients.

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BACKGROUND The prevalence of breast cancer is increasing at an alarming rate and thus demands exploration of most relevant diagnostic biomarkers. RAD50 is a cancer susceptibility gene which encodes a… Click to show full abstract

BACKGROUND The prevalence of breast cancer is increasing at an alarming rate and thus demands exploration of most relevant diagnostic biomarkers. RAD50 is a cancer susceptibility gene which encodes a DNA damage repairing protein. Its role in breast cancer as clinico-pathological specific biomarker has yet to be explored. OBJECTIVE This study was aimed to investigate the RAD50 expression and its promoter's methylation level variations in breast invasive carcinoma patients having different clinico-pathological features. This study further explored mutational spectrum of RAD50 and correlation of its expression with survival of patients and effectiveness of drugs used for treatment. METHOD Enrichment analysis of RAD50 was accomplished using platform of GeneCards. The information regarding RAD50 expression, its promoter methylation and impact on survival of patient was retrieved from TCGA and CPTAC databases. However, the effect of RAD50 expression on tumor's response to various drugs was deduced through analysis of CCLE and genomic of GDSC dataset. RESULTS The promoter hyper-methylation and elevated expression of RAD50 was documented in various subgroups of breast invasive carcinoma. The subjects having low/medium expression level were observed to survive longer than patients exhibiting high expression of RAD50 except post-menopausal subjects. The frequency of missense mutations was higher in RAD50 than truncating mutations. Most of the drugs were found to have positive correlation with RAD50 expression. CONCLUSION The status of RAD50 promoter's methylation inversely correlates with the expression level of RAD50. While RAD50 is overexpressed in breast cancer patients and thus makes tumor resistant against many anti-cancer drugs.

Keywords: cancer; rad50 expression; rad50; breast cancer

Journal Title: Current cancer drug targets
Year Published: 2020

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