Aldehyde Dehydrogenase 1 Expression Predicts Chemoresistance and Poor Clinical Outcomes in Patients with Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemotherapy Prior to Radical Hysterectomy.
BACKGROUND
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.|Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, People's Republic of China.
Qingsheng
Q
Xie
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.|Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, People's Republic of China.
Jinxiao
J
Liang
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Qunxian
Q
Rao
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Xiaofei
X
Xie
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Ruixin
R
Li
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Yunyun
Y
Liu
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Hui
H
Zhou
Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Jingjing
J
Han
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. yaoyaotingting@msn.com.
Tingting
T
Yao
Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. zhongqiu_lin@163.com.
Zhongqiu
Z
Lin
D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007044:Hysterectomy; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D016190:Carboplatin; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D002945:Cisplatin; D005472:Fluorouracil