Molecular markers of DNA damage and repair in cervical cancer patients treated with cisplatin neoadjuvant chemotherapy: an exploratory study
Neoadjuvant chemotherapy (NAC) is an important treatment strategy for cervical cancer; however, few predictive markers of the response to NAC exist. Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, is associated with chemoresistance in a variety of cancers. This study attempted to investigate the value of ALDH1 as a predictive marker of chemosensitivity and its prognostic value in cervical cancer patients treated with NAC. Immunohistochemistry was used to evaluate ALDH1 expression in matched pre- and post-NAC tumor samples from 52 patients with cervical cancer. Kaplan–Meier analysis and a Cox proportional hazards regression model were applied to determine overall survival (OS) and disease-free survival (DFS). Fourteen patients (26.9 %) had ALDH1-positive tumors pre-NAC, and ALDH1 expression pre-NAC was significantly associated with a low clinical chemotherapy response rate and clinical non-response. Twenty-two patients (42.3 %) had ALDH1-positive tumors post-NAC, and ALDH1 expression post-NAC was associated with poor DFS and OS (both p = 0.004). Multivariate analysis revealed that ALDH1 expression post-NAC was an independent prognostic factor for OS (hazard ratio 3.513; p = 0.033). Moreover, we observed that ALDH1 expression was increased after NAC in 18 patients (36.7 %). Increased levels of ALDH1 expression after NAC predicted poor DFS and OS (p = 0.013 and p = 0.08, respectively). Our findings suggest that ALDH1 expression pre-NAC may be a predictive marker for response to NAC, and ALDH1 expression post-NAC could be a prognostic marker for cervical cancer.