J Cancer 2018; 9(14):2472-2479. doi:10.7150/jca.25184

Research Paper

HE4 and eIF3a Expression Correlates with Surgical Outcome and Overall Survival in Ovarian Cancer Patients with Secondary Cytoreduction

Chen-Hui Luo1,2, Min Zhao2, Xiao-Yan Chen3, Shohreh Shahabi4, Wenan Qiang5, Liang Zeng6, Jing Wang7✉, Hong-Hao Zhou2✉

1. Laboratory Animal Research Center, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
2. Department of Clinical Pharmacology, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
3. Department of Pathology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
4. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Prentice Women's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
5. Center for Developmental Therapeutics, Chemistry of Life Processes Institute, Department of Obstetrics and Gynecology-Division of Reproductive Science in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
6. Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
7. Department of Gynecologic Oncology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.

Abstract

For recurrent ovarian cancer (ROC), secondary cytoreductive surgery (SCS) is recommended as one optional treatment. However, little is known about the expression and clinical significance of biomarkers during SCS. Human epididymis protein 4 (HE4) is a clinical biomarker for ovarian cancer. Eukaryotic translation initiation factor 3a (eIF3a) is investigated extensively as a potential biomarker for malignancy. The purpose of this study was to investigate the expressions of HE4 and eIF3a at SCS, as well as their associations with surgical outcome and survival in ROC patients. Immunohistochemistry was performed to determine the expressions of HE4 and eIF3a in ovarian tumors taken from both initial and secondary cytoreductive surgery of 35 ROC patients. eIF3a levels were significantly increased at SCS, compared to those at initial cytoreductive surgery (ICS), while HE4 levels were similar. Both HE4 and eIF3a expressions were associated with surgical outcome, in terms of residual tumor. For ICS, patients with high HE4 expression achieved a higher incidence of optimal cytoreduction than those with low HE4 expression (81.0% vs. 33.3%, P = 0.015). A similar result happened in SCS, indicated by higher incidence of no residual tumor in patients with high HE4 expression (76.4% vs. 44.4%, P = 0.046). And high HE4 expression at SCS was more likely to enhance surgical outcome of SCS (77.8% vs. 29.4%, P = 0.038). Therefore, high HE4 expression at either surgery is a predictor of better overall survival (OS) (P = 0.011 and 0.002). Furthermore, patients with an elevated total score (TS) of HE4 between the two surgeries tended to have prolonged OS, compared to those with a non-elevated TS of HE4 (P = 0.076). For eIF3a, initial eIF3a expression was associated with secondary residual tumor (P = 0.035), and the difference in eIF3a expression between the two surgeries correlated with OS (P = 0.052). The expressions of HE4 and eIF3a in tumor specimens correlated with surgical outcome and predicted OS in ROC patients with SCS, thus meriting further investigation.

Keywords: HE4, eIF3a, recurrent ovarian cancer (ROC), secondary cytoreductive surgery (SCS), residual tumor, overall survival

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How to cite this article:
Luo CH, Zhao M, Chen XY, Shahabi S, Qiang W, Zeng L, Wang J, Zhou HH. HE4 and eIF3a Expression Correlates with Surgical Outcome and Overall Survival in Ovarian Cancer Patients with Secondary Cytoreduction. J Cancer 2018; 9(14):2472-2479. doi:10.7150/jca.25184. Available from http://www.jcancer.org/v09p2472.htm