A combined ANXA2-NDRG1-STAT1 gene signature predicts response to chemoradiotherapy in cervical cancer

A combined ANXA2-NDRG1-STAT1 gene signature predicts response to\r\nchemoradiotherapy in cervical cancer.\r\n\r\nBACKGROUND: A better understanding of locally advanced cervical cancer (LACC) is \r\nmandatory for further improving the rates of disease control, since a significant\r\nproportion of patients still fail to respond or undergo relapse after concurrent \r\nchemoradiation treatment (CRT), and survival for these patients has generally\r\nremained poor.\r\nMETHODS: To identify specific markers of CRT response, we compared pretreatment\r\nbiopsies from LACC patients with pathological complete response (sensitive) with \r\nthose from patients showing macroscopic residual tumor (resistant) after\r\nneoadjuvant CRT, using a proteomic approach integrated with gene expression\r\nprofiling. The study of the underpinning mechanisms of chemoradiation response\r\nwas carried out through in vitro models of cervical cancer.\r\nRESULTS: We identified annexin A2 (ANXA2), N-myc downstream regulated gene 1\r\n(NDRG1) and signal transducer and activator of transcription 1 (STAT1) as\r\nbiomarkers of LACC patients' responsiveness to CRT. The dataset collected through\r\nqPCR on these genes was used as training dataset to implement a Random Forest\r\nalgorithm able to predict the response of new patients to this treatment.\r\nMechanistic investigations demonstrated the key role of the identified genes in\r\nthe balance between death and survival of tumor cells.\r\nCONCLUSIONS: Our results define a predictive gene signature that can help in\r\ncervical cancer patient stratification, thus providing a useful tool towards more\r\npersonalized treatment modalities.