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.

Fructose-1,6-bisphosphatase-1 decrease may promote carcinogenesis and chemoresistance in cervical cancer

“…Immunohistochemistry (IHC) assay. The 10x12 (120 cores) tissue microarray (TMA) was made by FUSCC Tissue Bank, as described previously (15). Each case has two cores made from separate sources.…”

“…We used the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay to detect in vitro inhibition rates of four platinum agents (cisplatin, carboplatin, nedaplatin and oxaliplatin), as described previously (15). Optical densities (OD 570 nm ) were measured by Microplate Reader (Bio-Rad 550; Bio-Rad Laboratories, Hercules, CA, USA).…”

Base excision repair pathway:PARP1genotypes as modulators of therapy response in cervical cancer patients

“…Previous studies have shown that therapy response can vary significantly among patients due to interindividual variations of DNA repair activity caused by the presence of genetic alterations in DNA repair genes which results in DNA repair deficiency and hence with chemoradiotherapy sensitization (Nogueira et al, 2012, de las Penas et al, 2006, Shi et al, 2012, Chung et al, 2006. Because of the importance of this process in determining sensitivity and resistance, components of the DNA damage repair pathways have been studied with regard to genetic variation and response to therapy (Hildebrandt et al, 2009).…”

Aberrant Expression of RAD52, Its Prognostic Impact in Rectal Cancer and Association with Poor Survival of Patients

“…It was speculated that low non-physiological levels of RAD52 could promote a dysregulated HDR and this could possibly up-regulate error-prone backup repair pathways. Another study [63] has found that low RAD52 expression is associated with a poor response of cervical cancer cells to carboplatin. It was suggested that RAD52 SNPs, either individually or collectively, could modify gene function and alter RAD52 protein expression levels, making the cervical cancer cell resistant to platinum agents.…”