Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, Brazil.
Exp Mol Pathol. 2011 Oct;91(2):584-9. doi: 10.1016/j.yexmp.2011.06.006. Epub 2011 Jul 12.
Esophageal squamous cell carcinoma (ESCC) is highly fatal due to late diagnosis and inefficient treatment. Early disease detection could improve diagnosis and patient survival. Esophageal squamous epithelial cells express SPRR3, a member of the small proline-rich protein family, which is downregulated in ESCC. Therefore, SPRR3 expression may be used as a biomarker to follow the transition from healthy mucosa to ESCC. Both SPRR3 mRNA splice variants, v1 and v2, were evaluated by real time PCR in tumor and histologically normal adjacent tissue biopsies from 84 ESCC patients and 18 healthy controls. SPRR3-v1 was most highly expressed in the esophageal mucosa of healthy subjects, with an increasingly lower expression in the adjacent mucosa of ESCC patients and in tumors, respectively. SPRR3-v2 expression was low in normal mucosa and in tumors but it was higher in the adjacent mucosa of ESCC patients. In addition, we found a significant correlation between a lower SPRR3-v1 and SPRR3-v2 expression and age and alcohol consumption, respectively. SPRR3 protein expression presented a good correlation with SPRR3 mRNA expression. Cut-off points to discriminate between healthy mucosa, tumor and adjacent mucosa were determined with receiver operating characteristic (ROC) curves. This analysis showed that SPRR3-v1 expression discriminates the esophageal mucosa of healthy subjects from the adjacent mucosa and the tumor of ESCC patients with high sensitivity and specificity. Our data shows that the quantitative analysis of SPRR3 mRNA is a robust and reliable method to monitor the malignant transformation of the healthy esophageal mucosa into ESCC.
食管鳞状细胞癌（ESCC）由于诊断较晚和治疗效果不佳而导致死亡率很高。早期疾病检测可以提高诊断率和患者生存率。食管鳞状上皮细胞表达 SPRR3，它是小富含脯氨酸蛋白家族的成员，在 ESCC 中表达下调。因此，SPRR3 表达可能被用作一种生物标志物，用于跟踪从健康黏膜向 ESCC 的转变。在 84 名 ESCC 患者和 18 名健康对照者的肿瘤和组织学正常相邻组织活检中，通过实时 PCR 评估了 SPRR3 mRNA 剪接变体 v1 和 v2。SPRR3-v1 在健康受试者的食管黏膜中表达最高，在 ESCC 患者的相邻黏膜和肿瘤中分别呈逐渐降低的表达。SPRR3-v2 在正常黏膜和肿瘤中表达较低，但在 ESCC 患者的相邻黏膜中表达较高。此外，我们发现 SPRR3-v1 和 SPRR3-v2 表达与年龄和饮酒量分别呈显著相关。SPRR3 蛋白表达与 SPRR3 mRNA 表达呈良好相关性。使用接收器操作特征（ROC）曲线确定区分健康黏膜、肿瘤和相邻黏膜的 SPRR3-v1 和 SPRR3-v2 表达的截断值。该分析表明，SPRR3-v1 表达以高灵敏度和特异性区分健康受试者的食管黏膜与 ESCC 患者的相邻黏膜和肿瘤。我们的数据表明，SPRR3 mRNA 的定量分析是监测健康食管黏膜向 ESCC 恶性转化的一种稳健可靠的方法。
