Expression of voltage-gated sodium channel Nav1.5 in non-metastatic colon cancer and its associations with estrogen receptor (ER)-β expression and clinical outcomes.

Expression of voltage-gated sodium channel Nav1.5 in non-metastatic colon cancer and its associations with estrogen receptor (ER)-β expression and clinical outcomes.
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DOI:
10.1186/s40880-017-0253-0
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发表时间:
2017-11-09
影响因子:
--
通讯作者:
Fang Y
Fang Y
中科院分区:
医学2区
文献类型:
--
作者:
Peng J;Ou Q;Wu X;Zhang R;Zhao Q;Jiang W;Lu Z;Wan D;Pan Z;Fang Y

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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。然而,Nav1.5表达的预后意义仍不确定。本研究旨在探讨Nav1.5表达与接受根治性切除术的非转移性结肠癌患者的临床结局和雌激素受体-β(ER-β)表达的相关性。总共选择了269例连续的经病理证实的I-III期结肠癌患者,这些患者接受了根治性切除术。采用免疫组织化学方法检测石蜡包埋组织芯片中Nav1.5和ER-β的表达。根据阳性染色细胞的百分比和强度确定IHC评分。采用X分块法、k系数、卡方检验或Fisher精确检验、逻辑回归、对数秩检验和考克斯比例风险模型进行统计学分析。我们发现Nav1.5在平均IHC评分较高的肿瘤组织中普遍表达(5.1 ± 3.5 vs. 3.5 ± 2.7,P < 0.001)。结肠癌组织中Nav1.5高表达与术前癌胚抗原水平高[OR = 2.980; 95%可信区间(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。Log-rank检验结果显示Nav1.5高表达导致结肠癌患者的5年无病生存率较低(77.2%vs.92.1%,P = 0.048),尤其是ER-β高表达肿瘤患者(76.2%vs.91.3%,P = 0.032)。考克斯比例风险模型分析显示,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不利的预后因素。Nav1.5的高表达与ER-β的高表达相关,并提示非转移性结肠癌患者的肿瘤学预后不良。
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.
DOI: 10.1038/ncomms11067
发表时间: 2016-04-11
影响因子: 16.6
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Freyermuth F;Rau F;Kokunai Y;Linke T;Sellier C;Nakamori M;Kino Y;Arandel L;Jollet A;Thibault C;Philipps M;Vicaire S;Jost B;Udd B;Day JW;Duboc D;Wahbi K;Matsumura T;Fujimura H;Mochizuki H;Deryckere F;Kimura T;Nukina N;Ishiura S;Lacroix V;Campan-Fournier A;Navratil V;Chautard E;Auboeuf D;Horie M;Imoto K;Lee KY;Swanson MS;de Munain AL;Inada S;Itoh H;Nakazawa K;Ashihara T;Wang E;Zimmer T;Furling D;Takahashi MP;Charlet-Berguerand N
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发表时间: 2013-11-01
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发表时间: 2015-02-01
期刊: MEDICAL HYPOTHESES
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