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RAD52 variants predict platinum resistance and prognosis of cervical cancer.

ABSTRACT: RAD52 is an important but not well characterized homologous recombination repair gene that can bind to single-stranded DNA ends and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. To evaluate the role of RAD52 variants in the response of tumor cells to platinum agents, we investigated their associations with platinum resistance and prognosis in cervical cancer patients. We enrolled 154 patients with cervical squamous cell carcinoma, who had radical surgery between 2008 and 2009, and genotyped three potentially functional RAD52 variants by the SNaPshot assay. We tested in vitro platinum resistance and RAD52 expression by using the MTT and immunohistochemistry methods, respectively. In 144 cases who had genotyping data, we found that both the rs1051669 variant and RAD52 protein expression were significantly associated with carboplatin resistance (P?=?0.024 and 0.028, respectively) and rs10774474 with nedaplatin resistance (P?=?0.018). The rs1051669 variant was significantly associated with RAD52 protein expression (adjusted OR?=?4.7, 95% CI?=?1.4-16.1, P?=?0.013). When these three RAD52 variants were combined, progression-free survival was lower in patients who carried at least one (?1) variant allele compared to those without any of the variant alleles (P?=?0.047). Therefore, both RAD52 variants and protein expression can predict platinum resistance, and RAD52 variants appeared to predict prognosis in cervical cancer patients. Large studies are warranted to validate these findings.

SUBMITTER: Shi TY

PROVIDER: S-EPMC3510183 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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RAD52 variants predict platinum resistance and prognosis of cervical cancer.

Shi Ting-Yan TY Yang Gong G Tu Xiao-Yu XY Yang Jing-Min JM Qian Ji J Wu Xiao-Hua XH Zhou Xiao-Yan XY Cheng Xi X Wei Qingyi Q

PloS one 20121129 11

RAD52 is an important but not well characterized homologous recombination repair gene that can bind to single-stranded DNA ends and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. To evaluate the role of RAD52 variants in the response of tumor cells to platinum agents, we investigated their associations with platinum resistance and prognosis in cervical cancer patients. We enrolled 154 patients with cervical squamous cell carcinoma, who had radical surge ...[more]

PMID: 23209746

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Project description:BACKGROUND Cervical cancer is one of the most common malignances among women globally. This study aimed to construct a novel immune-related signature to predict the prognosis and immune infiltration of cervical cancer. MATERIAL AND METHODS Transcriptomic profiles and corresponding clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database and GEO database. The hub immune-related genes were screened and selected using Cox regression analysis and LASSO regression analysis. A novel signature was established based on the expression levels and corresponding coefficients of the selected hub immune-related genes. Kaplan-Meier survival curve and ROC curve illustrated the prognostic value of this novel signature in cervical cancer. The predictive accuracy and stability of this novel signature were confirmed in the validation cohort, internal testing set and external testing set. Then, a nomogram was constructed to predict individual survival probability of cervical cancer patient. The association between the risk scores of novel signature and immune infiltration was investigated through single-sample gene set enrichment analysis (ssGSEA). RESULTS Ten hub immune-related genes (TFRC, SPP1, CAMP, CSF2, TUBB3, ZAP70, CHIT1, LEPR, DLL4, and DES) were selected to construct a novel signature. The risk score of this novel signature could be an independent prognostic factor in cervical cancer, which divided patients into high-risk and low-risk groups. The patients in high-risk groups showed significantly worse overall survival rates than those in low-risk groups in all training and validation cohorts (all P<0.05). A nomogram model was constructed based on the risk score of the novel signature and other clinical characteristics, which achieved the highest clinical net benefit across the entire range of reasonable threshold probabilities (concordance index=0.813). Furthermore, gene enrichment analysis revealed that the novel signature was closely related with immunology. The novel signature was negatively correlated with the infiltration of most immune cell types, especially T cell subsets (P<0.001). CONCLUSIONS The novel signature could comprehensively predict the prognosis and immune infiltration of cervical cancer. It may provide new insights for the precise treatment in cervical cancer.

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RAD52 variants predict platinum resistance and prognosis of cervical cancer.

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RAD52 variants predict platinum resistance and prognosis of cervical cancer.

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