Expression of circRNA ANKS1B and upstream transcription factor 1 in breast cancer tissues and its clinical significance
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摘要:目的
探讨乳腺癌组织中环状RNA ANKS1B(CircANKS1B)及上游转录因子1(USF1)的表达及其临床意义。
方法选取90例乳腺癌患者作为研究对象。采用免疫组织化学检测组织中USF1蛋白表达。采用荧光定量聚合酶链反应检测组织中CircANKS1B及USF1 mRNA的表达。分析癌组织中CircANKS1B与USF1 mRNA的相关性。分析CircANKS1B及USF1 mRNA表达与乳腺癌临床病理特征的关系。分析CircANKS1B及USF1 mRNA的表达与乳腺癌预后的关系。利用单因素及多因素COX比例风险模型分析乳腺癌预后的独立影响因素。
结果乳腺癌组织中USF1棕黄色阳性表达主要位于细胞核。乳腺癌组织中USF1蛋白表达阳性率为86.67%(78/90), 高于癌旁组织的15.56%(14/90), 差异有统计学意义(P＜0.001)。乳腺癌组织中CircANKS1B与USF1 mRNA的相对表达量分别为(4.12±0.68)、(6.35±1.21), 高于癌旁组织的(1.23±0.46)、(1.57±0.59), 差异有统计学意义(P＜0.001)。乳腺癌组织CircANKS1B与USF1 mRNA表达呈显著正相关(r=0.604, P＜0.001)。CircANKS1B与USF1 mRNA表达在不同肿瘤分期、淋巴结转移及是否三阴性乳腺癌方面比较, 差异具有统计学意义(P＜0.05)。CircANKS1B高表达患者中位生存时间为52.62个月(95%CI: 49.44~56.35), 短于CircANKS1B低表达患者的56.78个月(95%CI: 52.46~57.05), 差异有统计学意义(P=0.045)。USF1 mRNA低表达患者中位生存时间为52.53个月(95%CI: 48.83~56.23), 短于USF1 mRNA低表达患者的56.75个月(95%CI: 54.07~59.43), 差异有统计学意义(P=0.014)。CircANKS1B高表达、USF1 mRNA高表达、肿瘤分期Ⅲ期及合并淋巴结转移是乳腺癌预后的独立影响因素。
结论乳腺癌组织中CircANKS1B及USF1表达升高，二者与肿瘤TNM分期、淋巴结转移有关，可作为新的乳腺癌预后标志物。
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关键词:
- 乳腺癌 /
- 环状RNA ANKS1B /
- 上游转录因子1 /
- 生物标志物
Abstract:ObjectiveTo investigate the expression and clinical significance of CircRNA ANKS1B (CircANKS1B) and upstream transcription factor 1 (USF1) in breast cancer tissues.
MethodsA total of 90 patients with breast cancer were selected as subjects. USF1 protein expression in tissues was detected by immunohistochemistry. The expression of CircANKS1B and USF1 mRNA in tissues was detected by real-time quantitative polymerase chain reaction. The correlation between CircANKS1B and USF1 mRNA in cancer tissues was analyzed. The relationships of CircANKS1B and USF1 mRNA expression with clinicopathologic features of breast cancer were analyzed. The relationships of CircANKS1B and USF1 mRNA expression with prognosis of breast cancer were analyzed. Univariate and multivariate COX proportional risk models were used to analyze the independent influencing factors of the prognosis of breast cancer.
ResultsThe brownish-yellow expression of USF1 in breast cancer tissues was mainly located in the nucleus. The positive rate of USF1 protein expression in breast cancer tissues was 86.67% (78/90), which was significantly higher than 15.56% (14/90) in adjacent tissue (P < 0.001). The relative expression levels of CircANKS1B and USF1 mRNA in the breast cancer tissues were (4.12±0.68) and (6.35±1.21), respectively, which were significantly higher than (1.23± 0.46) and (1.57±0.59) in the adjacent tissue (P < 0.001). There was a significant positive correlation between CircANKS1B and USF1 mRNA expression in breast cancer tissues (r=0.604, P < 0.001). The expression of CircANKS1B and USF1 mRNA showed statistically significant differences in different tumor stages, lymph node metastasis and triple-negative breast cancer (P < 0.05). The median survival time of patients with high CircANKS1B expression was 52.62 months (95%CI, 49.44 to 56.35), which was significantly shorter than 56.78 months (95%CI: 52.46 to 57.05) in patients with low CircANKS1B expression (P=0.045). The median survival time of patients with low expression of USF1 mRNA was 52.53 months (95%CI, 48.83 to 56.23), which was significantly shorter than 56.75 months (95%CI, 54.07 to 59.43) of patients with low USF1 mRNA expression (P=0.014). CircANKS1B high expression, USF1 mRNA high expression, tumor stage Ⅲ and lymph node metastasis are independent influencing factors of the prognosis of breast cancer.
ConclusionThe expressions of CircANKS1B and USF1 are increased in breast cancer tissues, and correlated with TNM stage, lymph node metastasis, and are new breast cancer prognostic tumor markers.
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Keywords:
- breast cancer /
- circRNA ANKS1B /
- upstream transcription factor 1 /
- biomarker
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表 1 CircANKS1B、USF1 mRNA表达与乳腺癌临床病理特征的关系(x±s)
临床参数 分类 n CircANKS1B χ2 P USF1 mRNA χ2 P 年龄 ＜60岁 38 3.99±0.73 1.587 0.116 6.14±1.42 1.328 0.188 ≥60岁 52 4.22±0.64 6.50±1.15 肿瘤直径 ≥2 cm 37 4.25±0.75 1.543 0.126 6.46±1.24 0.740 0.462 ＜2 cm 53 4.03±0.60 6.27±1.17 组织学分型 黏液腺癌 21 4.15±0.69 0.031 0.969 6.31±1.23 0.011 0.989 浸润性小叶癌 22 4.10±0.67 6.36±1.22 浸润性导管癌 47 4.12±0.64 6.35±1.18 组织学分级 Ⅰ~Ⅱ级 60 4.10±0.61 0.409 0.483 6.19±1.14 1.812 0.073 Ⅲ级 30 4.16±0.74 6.67±1.27 肿瘤分期 Ⅰ~Ⅱ期 62 3.63±0.60 10.478 ＜0.001 5.55±1.03 9.700 ＜0.001 Ⅲ期 28 5.18±0.75 8.12±1.42 淋巴结转移 有 57 3.72±0.64 7.263 ＜0.001 7.69±1.15 13.210 ＜0.001 无 33 4.81±0.76 4.04±1.44 三阴性乳腺癌 是 18 4.56±0.70 3.162 ＜0.001 7.67±1.26 5.201 ＜0.001 否 72 4.01±0.65 6.02±1.19 
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表 2 影响乳腺癌预后的单因素Cox回归分析
因素 赋值 β SE Wald χ2 P HR 95%CI 年龄 1=≥60岁, 0=＜60岁 0.141 0.130 1.176 0.642 1.151 0.892~1.486 肿瘤大小 1=≥2 cm, 0=＜2 cm 0.174 0.149 1.364 0.514 1.191 0.889~1.594 病理类型 1=浸润性小叶癌及导管癌, 0=黏液腺癌 0.259 0.190 1.858 0.319 1.296 0.892~1.880 三阴性 1=是, 0=否 0.224 0.187 1.435 0.441 1.251 0.867~1.805 组织学分级 1=Ⅲ级, 0=Ⅰ~Ⅱ级 0.249 0.212 1.283 0.309 1.380 0.847~1.944 淋巴结转移 1=有, 0=无 0.471 0.151 8.249 ＜0.001 1.352 0.913~1.882 肿瘤分期 1=Ⅲ期, 0=Ⅰ~Ⅱ期 0.566 0.196 9.276 ＜0.001 1.730 1.434~2.099 CircANKS1B 1=高表达, 0=低表达 0.641 0.181 11.667 ＜0.001 2.041 1.813~2.463 USF1 mRNA 1=高表达, 0=低表达 0.717 0.214 12.696 ＜0.001 2.060 1.921~2.279
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表 3 影响乳腺癌患者预后的多因素Cox回归分析
因素 β SE Wald χ2 P HR 95%CI 淋巴结转移 0.970 0.420 5.339 0.006 2.637 1.158~6.008 肿瘤分期 0.680 0.235 8.373 ＜0.001 1.973 1.245~3.129 CircANKS1B 0.910 0.280 10.563 ＜0.001 2.484 1.435~4.301 USF1 mRNA 0.565 0.231 8.287 ＜0.001 1.660 1.236~3.058
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