Role of high ubiquitin-conjugating enzyme E2 expression as a prognostic factor in nasopharyngeal carcinoma

Wan-Chen Kao; Shih-Han Hsu; Chien-Liang Lin; Cheng-Yao Lin; Shang-Wen Chen; Yan-Xun Chen; Chao-Hsun Chen; Sung-Wei Lee; Chao-Jung Tsao; Wen-Tsung Huang; Shang-Hung Chen; Sheng-Yen Hsiao

doi:10.3892/ol.2022.13314

Role of high ubiquitin-conjugating enzyme E2 expression as a prognostic factor in nasopharyngeal carcinoma

Oncol Lett. 2022 Jun;23(6):194. doi: 10.3892/ol.2022.13314. Epub 2022 Apr 29.

Authors

Affiliations

¹ Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736402, Taiwan, R.O.C.
² National Institute of Cancer Research, National Health Research Institutes, Tainan 704016, Taiwan, R.O.C.
³ Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan 736402, Taiwan, R.O.C.
⁴ Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan, R.O.C.
⁵ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan, R.O.C.

Abstract

The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile (GSE12452 and GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.

Keywords: chemoradiotherapy; cisplatin; nasopharyngeal carcinoma; ubiquitin-conjugating enzyme E2 B.

Grants and funding

This work was supported by grants from Chi Mei Medical Center, Liouying (grant nos. CLFHR10806 and CLFHR10929) and the Ministry of Science and Technology, Taiwan (grant no. MOST 109-2314-B-384-009).