Zeng Jun, Shi Rong, Cai Cui-Xia, Liu Xin-Rui, Song Yan-Bin, Wei Min, Ma Wen-Li
Institute of Genetic Engineering, Southern Medical University, No.1838, Baiyun Road North, Guangzhou, People's Republic of China.
Cancer Cell Int. 2015 Jun 20;15:63. doi: 10.1186/s12935-015-0215-z. eCollection 2015.
Sineoculis homeobox homolog 1 (Six1), normally a developmentally restricted transcriptional regulator, is frequently dysregulated in mutiple cancers. Increasing evidences show that overexpression of Six1 plays a key role in tumorigenesis. However, the Six1 expression status and its relationship with the clinicopathological characteristics in prostate cancer were unclear. In this study, the mRNA and protein levels of Six1 in prostate cancer tissues and normal prostate tissues were evaluated. The clinicopathological significance of Six1 was investigated by immunohistochemistry (IHC) on a prostate cancer tissue microarray. The cut-off score for high expression of Six1 was determined by the receiver-operating characteristic (ROC) analysis. The correlation between Six1 protein expression and clinicopathological characteristics of prostate cancer was analyzed by Chi-square test. Increased expression of Six1 protein was observed in the majority of prostate cancer, compared with their paired adjacent normal prostate tissues. When Six1 high expression percentage was determined to be above 55 % (area under ROC curve = 0.881, P = 0.000), high expression of Six1 was observed in 55.6 % (80/144) of prostate cancer tissues and low expression of Six1 was observed in all normal prostate tissues by IHC. Increased expression of Six1 in patients was correlated with high histological grade (χ2 = 58.651, P = 0.00), advanced clinical stage (χ2 = 57.330, P = 0.000), high Gleason score (χ2 = 63.480, P = 0.000), high primary tumor grade (χ2 = 57.330, P = 0.000) and positive regional lymph node metastasis (χ2 = 19.294, P = 0.000). Furthermore, univariate and multivariate survival analysis suggested that Six1 was an independent prognostic indicator for overall survival (P < 0.05). This study suggests that Six1 could be served as an additional biomarker in identifying prostate cancer patients at risk of tumor progression, might potentially be used for predicting survival outcome of patients with prostate cancer.
眼 sineoculis 同源盒 1(Six1)通常是一种在发育过程中受到限制的转录调节因子,在多种癌症中经常发生失调。越来越多的证据表明,Six1 的过表达在肿瘤发生中起关键作用。然而,Six1 在前列腺癌中的表达状态及其与临床病理特征的关系尚不清楚。在本研究中,评估了 Six1 在前列腺癌组织和正常前列腺组织中的 mRNA 和蛋白质水平。通过对前列腺癌组织芯片进行免疫组织化学(IHC)研究 Six1 的临床病理意义。通过接受者操作特征(ROC)分析确定 Six1 高表达的临界分数。采用卡方检验分析 Six1 蛋白表达与前列腺癌临床病理特征之间的相关性。与配对的相邻正常前列腺组织相比,在大多数前列腺癌中观察到 Six1 蛋白表达增加。当 Six1 高表达百分比确定为高于 55%(ROC 曲线下面积=0.881,P = 0.000)时,通过 IHC 在 55.6%(80/144)的前列腺癌组织中观察到 Six1 高表达,而在所有正常前列腺组织中均观察到 Six1 低表达。患者中 Six1 表达增加与高组织学分级(χ2 = 58.651,P = 0.00)、晚期临床分期(χ2 = 57.330,P = 0.000)、高 Gleason 评分(χ2 = 63.480,P = 0.000)、高原发肿瘤分级(χ2 = 57.330,P = 0.000)和阳性区域淋巴结转移(χ2 = 19.294,P = 0.000)相关。此外,单因素和多因素生存分析表明,Six1 是总生存的独立预后指标(P < 0.05)。本研究表明,Six1 可作为识别有肿瘤进展风险的前列腺癌患者的额外生物标志物,可能潜在地用于预测前列腺癌患者的生存结果。