Excision repair cross-complementing group 2 upregulation is a potential predictive biomarker for oral squamous cell carcinoma recurrence

Abstract

Oral cancer is the fourth most common type of cancer among males in Taiwan, and the prognosis for patients with advanced-stage oral squamous cell carcinoma (OSCC) remains poor. The present study investigated the prognostic value of three DNA repair genes, namely excision repair cross-complementing group 1 (ERCC1), ERCC2 and X-ray repair cross-complementing group 1 (XRCC1) in OSCC. The protein expression levels of XRCC1, ERCC1 and ERCC2 in oral cell lines were analyzed via western blotting and immunohistochemistry using samples from 98 patients with biopsy-proven OSCC, while the χ² test was used to analyze the clinicopathological association. Kaplan-Meier estimates were used to determine the prognostic value of XRCC1, ERCC1 and ERCC2 for overall survival, and the log-rank test was used to evaluate the significance of differences. Multivariate analysis revealed a positive association between ERCC2 expression and OSCC recurrence (19.64-fold; 95% CI, 5.00-77.1; P<0.001). In addition, the high protein expression levels of XRCC1, ERCC1 and ERCC2 were associated with poor disease-free and overall survival rates. Therefore, the present study suggested that high ERCC2 expression may be a risk factor for OSCC recurrence.

Keywords: DNA repair; X-ray repair cross-complementing group 1; excision repair cross-complementing group 1; excision repair cross-complementing group 2; oral squamous cell carcinoma.

Figure 1.

XRCC1, ERCC1 and ERCC2 protein expression in primary oral epithelial cells, oral pre-cancer cells and various oral cancer cells. The cell lysates extracted from HOK primary oral epithelial cells, DOK oral pre-cancer cells and oral cancer cell lines, including SAS, OECM1, HSC-3 and Cal-27, underwent western blotting for detecting the expression levels of XRCC1, ERCC1 and ERCC2. Glioblastoma U87MG cell line served as a positive control. The numbers correspond to the grey density values of a single replicate. XRCC1, X-ray repair cross-complementing group 1; ERCC1/2, excision repair cross-complementing group 1/2.

Figure 2.

Immunohistochemical staining of XRCC1, ERCC1 and ERCC2 expression in OSCC tissues. ERCC1, ERCC2 or XRCC1 expression in oral normal tissues and cancer tissues, determined by immunohistochemistry, was divided into 4 categories according to the staining intensity: Score 0, no staining; score 1, weak staining; score 2, moderate staining; and score 3, strong staining. Original magnification, ×200. XRCC1, X-ray repair cross-complementing group 1; ERCC1/2, excision repair cross-complementing group 1/2; OSCC, oral squamous cell carcinoma.

Figure 3.

Disease-free survival and overall survival rates of patients with oral squamous cell carcinoma divided in low and high XRCC1, ERCC1 and ERCC2 expression groups. Survival curves were generated using the Kaplan-Meier method and the P-values were calculated using the log-rank test. XRCC1, X-ray repair cross-complementing group 1; ERCC1/2, excision repair cross-complementing group 1/2.