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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

  • Gynecologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgment

The authors would like to thank Dr. Bo Wang for his technical support. This work was supported by the National Natural Science Foundation of China (30672221, 30872743).

Conflict of interest

Qingsheng Xie, Jinxiao Liang, Qunxian Rao, Xiaofei Xie, Ruixin Li, Yunyun Liu, Hui Zhou, Jingjing Han, Tingting Yao, and Zhongqiu Lin declare that they have no actual or potential competing financial interests.

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Authors and Affiliations

  1. Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

    Qingsheng Xie PhD, Jinxiao Liang PhD, Qunxian Rao PhD, Xiaofei Xie MD, Ruixin Li MD, Yunyun Liu MD, Hui Zhou MD, Tingting Yao PhD & Zhongqiu Lin MD

  2. 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 Xie PhD & Jinxiao Liang PhD

  3. Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

    Jingjing Han MD

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  1. Qingsheng Xie PhD
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  2. Jinxiao Liang PhD
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Correspondence to Tingting Yao PhD or Zhongqiu Lin MD.

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Fig. S1

Identification and grading of ALDH1-positive tumor cells using immunohistochemistry. Representative images of (A) cervical cancer tissues with an ALDH1 score of 0; (B) 1+; (C) 2+; (D) and 3+; original magnification ×400. ALDH1 staining was mainly localized to the cytoplasm of the tumor cells, though faint expression was also observed in the surrounding stromal and vascular areas of the tumour tissues. Supplementary material 1 (TIFF 1985 kb)

Fig. S2

Kaplan-Meier 5-year disease-free survival (DFS) and 5-year overall survival (OS) curves for patients with cervical cancer. (A and B) Patients with ALDH1-positive tumors pre-NAC tended to have poorer DFS and OS, though this difference was not significant. (C and D) Patients who responded to NAC had significantly better DFS and OS. (E and F) Patients with ALDH1-positive tumors post-NAC had poorer 5-year DFS and 5-year OS. (G and H) Patients with increased ALDH1 expression after NAC had poorer DFS and OS than non-increased ones; however, this effect was not significant for DFS. Supplementary material 2 (TIFF 984 kb)

Supplementary material 3 (DOC 64 kb).

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Xie, Q., Liang, J., Rao, Q. et al. 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. Ann Surg Oncol 23, 163–170 (2016). https://doi.org/10.1245/s10434-015-4555-7

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