比较基因组杂交技术分析食管鳞状细胞癌遗传变异及PPFIA1异常表达的临床意义

Analysis of the genetic variation of esophageal squamous cell carcinoma via comparative genomic hybridization and clinical significance of abnormal PPFIA1 expression

摘要:

目的 分析食管鳞状细胞癌中基因组的遗传学变异特征，探讨异常扩增基因PPFIA1与临床病理参数及预后的相关性。方法 选取2014年3月—2014年7月新疆医科大学第一附属医院食管鳞状细胞癌患者手术切除的6对肿瘤组织及癌旁正常组织。采用比较基因组杂交技术（CGH）检测食管鳞状细胞癌患者基因组遗传学变化，免疫组织化学法检测异常扩增基因PPFIA1在食管鳞状细胞癌中的表达水平，分析PPFIA1基因与食管鳞状细胞癌病理参数及预后的相关性。结果 CGH分析结果发现食管鳞状细胞癌患者中5号染色体p15.33和11号染色体的q13.3和q22.1变异较大。食管癌组织PPFIA1阳性表达率高于癌旁组织（P <0.05）。不同临床分期、淋巴结转移食管癌患者的PPFIA1高表达率比较，差异有统计学意义（P <0.05），临床分期越高PPFIA1的阳性表达率也越高，淋巴结有转移的患者PPFIA1的阳性表达率高于无淋巴结转移的患者。而不同性别、年龄、病理分级、分化类型、肿瘤大小、浸润深度食管癌患者的PPFIA1高表达率比较，差异无统计学意义（P >0.05）。PPFIA1高表达与低表达患者生存曲线比较，差异有统计学意义（P <0.05），PPFIA1高表达患者生存期较短，预后较差。结论 食管鳞状细胞癌中11q13.3变异较大，PPFIA1基因可能在食管鳞状细胞癌的转移和预后中起一定作用。

Abstract:

Objective To analyze the genomic variation of esophageal squamous cell carcinoma, and to explore the correlations between the abnormal PPFIA1 expression and clinicopathological characteristics and prognosis.Methods Six pairs of tumor and adjacent tissues surgically removed from patients with esophageal squamous cell carcinoma in the First Affiliated Hospital of Xinjiang Medical University from March 2014 to July 2014 were collected. The genomic changes in these samples were detected via comparative genomic hybridization (CGH), and the expression of the abnormally amplified gene PPFIA1 in esophageal squamous cell carcinoma was detected by immunohistochemistry. The correlations between the gene expression of PPFIA1 and pathological parameters of esophageal squamous cell carcinoma and prognosis were analyzed.Results The CGH analyses showed that the variations were pronounced within p15.33 of Chromosome 5 and q13.3 and q22.1 of Chromosome 11 in patients with esophageal squamous cell carcinoma. Immunohistochemical results verified that the positive expression rate of PPFIA1 in esophageal cancer tissues was higher than that in the adjacent tissues (P < 0.05). There were differences in the positive expression rate of PPFIA1 among esophageal squamous cell carcinoma patients with different clinical stage and between those with and without lymph node metastasis (P < 0.05). Specifically, the positive expression rate of PPFIA1 was higher in those with advanced clinical stage and with lymph node metastasis (P < 0.05). There was no statistical difference in the positive expression rate of PPFIA1 among esophageal squamous cell carcinoma patients with different gender, age, and pathological grade, degree of differentiation, size and depth of invasion of tumors. The survival curves were different among patients with high and low expressions of PPFIA1 (P < 0.05), and those with positive PPFIA1 expression had a shorter survival duration and a worse prognosis.Conclusions 11q13.3 variation is significant in esophageal squamous cell carcinoma, and PPFIA1 may play a role in the metastasis and prognosis of esophageal squamous cell carcinoma.