ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines

Following validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC, ABCC5/GTF2H2, ERCC2/GTF2H2, XPA/XPC and XRCC1/XPC. All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was (ABCC5/GTF2H2, ERCC2/GTF2H2) with an R2 value of 0.96 (p < 0.001).These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.Non-small cell lung cancer (NSCLC) is the most common type of bronchogenic carcinoma. Although chemotherapeutic regimens with greater efficacy continue to be developed, the best regimens presently give an overall response rate of only 30–50%. Lack of response is attributable to resistance that is present de novo or develops in response to treatment. If the resistance to drugs could be surmounted or if the most effective drug candidates for treatment could be better determined, the impact in terms of survival would be substantial. Because mechanisms of chemoresistance likely involve multiple gene products, we hypothesize that patterns of individual gene expression and/or indices comprising the expression values of multiple genes will provide more effective markers of chemoresistant NSCLC tumors than values of individual genes.Currently, cisplatin and carboplatin are among the most widely used cytotoxic anticancer drugs. However, resistance to these drugs through de novo or induced mechanisms undermines their curative potential [1]. Recently, understanding regarding potential modes of chemoresistance to platinum compounds has been obtained through studies correlating cytotoxicity with nucleotide excision-repair (NER) [2-7] or drug uptake/efflux [7-13]. In this study, we investigated whether de novo gene expression differences are correlated with a predisposition of NSCLC tumors to chemoresistance.Current advances in technology, including microarra