A 7 gene expression score predicts for radiation response in cancer cervix

Abstract

BackgroundCervical cancer is the most common cancer among Indian women. The current recommendations are to treat the stage IIB, IIIA, IIIB and IVA with radical radiotherapy and weekly cisplatin based chemotherapy. However, Radiotherapy alone can help cure more than 60% of stage IIB and up to 40% of stage IIIB patients.MethodsArchival RNA samples from 15 patients who had achieved complete remission and stayed disease free for more than 36 months (No Evidence of Disease or NED group) and 10 patients who had failed radical radiotherapy (Failed group) were included in the study. The RNA were amplified, labelled and hybridized to Stanford microarray chips and analyzed using BRB Array Tools software and Significance Analysis of Microarray (SAM) analysis. 20 genes were selected for further validation using Relative Quantitation (RQ) Taqman assay in a Taqman Low-Density Array (TLDA) format. The RQ value was calculated, using each of the NED sample once as a calibrator. A scoring system was developed based on the RQ value for the genes.ResultsUsing a seven gene based scoring system, it was possible to distinguish between the tumours which were likely to respond to the radiotherapy and those likely to fail. The mean score ± 2 SE (standard error of mean) was used and at a cut-off score of greater than 5.60, the sensitivity, specificity, Positive predictive value (PPV) and Negative predictive value (NPV) were 0.64, 1.0, 1.0, 0.67, respectively, for the low risk group.ConclusionWe have identified a 7 gene signature which could help identify patients with cervical cancer who can be treated with radiotherapy alone. However, this needs to be validated in a larger patient population.

Oncogenic Function of SCCRO5/DCUN1D5 Requires Its Neddylation E3 Activity and Nuclear Localization

“…Guo and colleagues suggest that SCCRO5 may be involved in regulating ubiquitination of the proteins involved in DNA-damage repair (20). Consistent with this suggestion, SCCRO5 was found to be part of a panel of seven genes whose expression score predicts radiation response in patients with cervical cancer (47). Further work is required to define the CRLs and protein targets that are dependent on SCCRO5 in the DNA-damage response, cellular activities, and oncogenesis.…”

Dominant negative Ubiquitin-conjugating enzyme E2C sensitizes cervical cancer cells to radiation

“…We have recently shown that, UBE2C is over expressed in cervical cancer (Rajkumar et al 2011) and it is one among the seven-gene signature whose expression pattern could help identify patients to be treated with radiotherapy alone (Rajkumar et al 2009). Our study had shown the SiHa cells expressing the DN-UBE2C to have growth inhibition, relative to the parental and the vector-only transfected SiHa cells (Rajkumar et al 2011).…”

Identification and validation of genes involved in gastric tumorigenesis

“…Triplicate cDNA template samples were amplified and analysed on the ABI Prism 7900HT sequence detection system (Applied Biosystems, Foster City, CA) as described earlier [18]. …”