摘要
目的 探讨结直肠癌(colorectal cancer,CRC)中特异蛋白1(specificity protein 1,SP1)表达的瘤内异质性(intratumor heterogeneity,ITH)及其临床意义.方法 收集CRC临床标本,采用免疫组化EnVision法检测SP1蛋白的表达水平及模式,明确SP1蛋白表达的ITH特征,定义SP1蛋白的ITH水平,并分析SP1蛋白ITH水平与CRC患者临床病理特征及预后的关系.结果 在CRC中SP1蛋白呈典型的ITH表达特征,其ITH水平与淋巴结转移(P<0.001)和TNM分期(P<0.001)相关.生存分析表明,SP1蛋白高ITH患者的总生存期(overall survival,OS)显著低于SP1蛋白低ITH患者(61.25%vs 81.82%),差异有统计学意义(P=0.004).单因素和多因素Cox回归分析显示,SP1蛋白高ITH是CRC患者不良O S(HR=2.680,P=0.017)的独立预测因子.结论 CRC中SP1蛋白的表达具有显著的ITH特征,并首次定义了 SP1 ITH水平的量化标准,证实SP1蛋白高ITH与CRC进展及不良预后显著相关.
Abstract
Objective To investigate the intratumor heterogeneity(ITH)of specificity protein 1(SP1)protein expres-sion in colorectal cancer(CRC)and its clinical significance.Methods Clinical specimens of CRC were collected.The expression level and pattern of SP1 protein were detected by immunohistochemical EnVision method.The ITH character-istics of SP1 protein expression were identified,and the ITH level of SP1 protein was defined.The relationship between ITH level of SP1 protein and clinicopathological characteristics and prognosis of CRC patients was analyzed.Results SP1 protein showed typical ITH expression in CRC.The ITH level of SP1 protein was associated with lymph node me-tastasis(P<0.001)and TNM stage(P<0.001).Survival analysis showed that the overall survival(OS)of patients with high ITH level of SP1 protein was significantly lower than that with low ITH level(61.25%vs 81.82%,P=0.004).Univariate and multivariate Cox regression analyses showed that high SP1 protein ITH was an independent pre-dictor of poor OS in CRC patients(HR=2.680,P=0.017).Conclusion The expression of SP1 protein in CRC has significant ITH characteristics,and defines the quantitative criteria of SP1 ITH level for the first time.It is demonstrated that a high ITH level of SP1 protein is significantly associated with CRC progression and poor prognosis.