Peng Jianhong, Ou Qingjian, Wu Xiaojun, Zhang Rongxin, Zhao Qian, Jiang Wu, Lu Zhenhai, Wan Desen, Pan Zhizhong, Fang Yujing
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
Chin J Cancer. 2017 Nov 9;36(1):89. doi: 10.1186/s40880-017-0253-0.
Voltage-gated sodium channel 1.5 (Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β (ER-β) expression in non-metastatic colon cancer patients receiving radical resection.
A total of 269 consecutive patients with pathologically confirmed stages I-III colon cancer who underwent radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry (IHC) on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coefficient, Chi square test or Fisher's exact test, logistic regression, log-rank test, and Cox proportional hazards models.
We found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues (5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001). The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio (OR) = 2.980; 95% confidential interval (CI) 1.163-7.632; P = 0.023] and high ER-β expression (OR = 2.808; 95% CI 1.243-6.343; P = 0.013). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival (DFS) rate in colon cancer patients (77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor (76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression [hazard ratio (HR) = 2.738; 95% CI 1.100-6.819; P = 0.030] and lymph node metastasis (HR = 2.633; 95% CI 1.632-4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer patients.
High expression of Nav1.5 was associated with high expression of ER-β and indicated unfavorable oncologic prognosis in patients with non-metastatic colon cancer.
电压门控钠通道1.5（Nav1.5）可能促进结肠癌细胞的迁移和侵袭行为。迄今为止，Nav1.5表达的预后意义仍未确定。本研究旨在探讨接受根治性切除的非转移性结肠癌患者中Nav1.5表达与临床结局及雌激素受体-β（ER-β）表达之间的关联。
选取269例连续的经病理确诊为I-III期结肠癌且接受根治性切除的患者。通过免疫组织化学（IHC）检测由石蜡包埋标本构建的组织芯片上的Nav1.5和ER-β表达。根据阳性染色细胞的百分比和强度确定IHC评分。采用X-tile法、k系数、卡方检验或Fisher精确检验、逻辑回归、对数秩检验和Cox比例风险模型进行统计分析。
我们发现Nav1.5在肿瘤组织中普遍表达，与配对的肿瘤旁正常组织相比，其平均IHC评分更高（5.1±3.5 vs. 3.5±2.7，P<0.001）。结肠癌组织中Nav1.5的高表达与术前癌胚抗原水平升高[比值比（OR）=2.980；95%置信区间（CI）1.163-7.632；P=0.023]和ER-β高表达（OR=2.808；95%CI 1.243-6.343；P=0.013）相关。对数秩检验结果显示，Nav1.5高表达导致结肠癌患者5年无病生存率（DFS）较低（77.2% vs. 92.1%，P=0.048），尤其是在ER-β高表达肿瘤患者中（76.2% vs. 91.3%，P=0.032）。Cox比例风险模型分析表明，Nav1.5高表达[风险比（HR）=2.738；95%CI 1.100-6.819；P=0.030]和淋巴结转移（HR=2.633；95%CI 1.632-4.248；P<0.001）是结肠癌患者DFS不良的预后因素。
Nav1.5高表达与ER-β高表达相关，提示非转移性结肠癌患者的肿瘤预后不良。
