Liu Jun, Lin Yongping, Yang Haihong, Deng Qiuhua, Chen Guoqin, He Jianxing
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Rd, Guangzhou, 510120, Guangdong Province, People's Republic of China.
Tumour Biol. 2011 Dec;32(6):1113-21. doi: 10.1007/s13277-011-0211-4. Epub 2011 Jul 22.
The purpose of this study was to investigate the expressions of tumor inhibitor of growth (ING1) gene p33ING1, p53, and autophagy-related gene Beclin1 in human non-small cell lung cancer (NSCLC), and the correlation between their expressions with clinical pathological features and clinical significance. The research can provide new ideas and experimental evidence for early diagnosis and biotherapy for NSCLC in the future. The human NSCLC tissues and surrounding non-cancerous tissues were collected from surgical operation. The expressions of mRNA or protein of p33ING1, p53, and Beclin1 were detected by using of reverse transcription polymerase chain reaction or Western blot in these tissues. The results were used to analyze the relationships between these gene expressions with the developing of NSCLC and clinical pathological features. The expressions of mRNA or protein of p33ING1 and Beclin1 in NSCLC tissues were significantly lower than that in surrounding noncancerous tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in well- and middle-differentiated NSCLC tissues were lower than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in presence of lymph nodes metastasis were lower than those in absence of lymph nodes metastasis (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in patients of pathological stage (stages I-II) were higher than those in pathological stage (stages III-IV) (p < 0.05). But the expression of protein of mutant-type p53 in NSCLC tissues was significantly higher than that in surrounding non-cancerous tissues (p < 0.05). The expressions of protein of mutant-type p53 in well- and middle-differentiated NSCLC tissues were higher than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of protein of mutant-type p53 in presence of lymph nodes metastasis were higher than those in absence of lymph nodes metastasis (p < 0.05). The expressions of protein of mutant-type p53 in patients of pathological stage (stages I-II) were lower than those in pathological stage (stages III-IV) (p < 0.05). These expression changes of p33ING1, p53, and autophagy-related Beclin1 genes were associated with tumor cell differentiation, lymph nodes metastasis, and pathological stage of NSCLC. But these expression changes of these three genes were not associated with gender, age, size of primary carcinoma, histological type of NSCLC (p > 0.05). The expression of mRNA of p53 and Beclin1 were correlated with p33ING1 mRNA expression in NSCLC tissues (p < 0.05). The activity changes of tumor inhibitor of growth, autophagy, and apoptosis may be related to the emergence and the development of NSCLC. The combined detection of p33ING1, p53, and Beclin1 genes and proteins will be helpful for early diagnosis and prognosis judgment for NSCLC, and can provide experimental evidence for biotherapy of NSCLC.
本研究旨在探讨生长抑制因子（ING1）基因p33ING1、p53及自噬相关基因Beclin1在人非小细胞肺癌（NSCLC）中的表达情况，以及它们的表达与临床病理特征之间的相关性及临床意义。该研究可为未来NSCLC的早期诊断和生物治疗提供新思路和实验依据。收集手术切除的人NSCLC组织及周围非癌组织，采用逆转录聚合酶链反应或蛋白质免疫印迹法检测这些组织中p33ING1、p53及Beclin1的mRNA或蛋白表达情况，分析这些基因表达与NSCLC发生发展及临床病理特征的关系。NSCLC组织中p33ING1和Beclin1的mRNA或蛋白表达显著低于周围非癌组织（p＜0.05）。高分化和中分化NSCLC组织中p33ING1和Beclin1的mRNA或蛋白表达低于低分化NSCLC组织（p＜0.05）。有淋巴结转移的NSCLC组织中p33ING1和Beclin1的mRNA或蛋白表达低于无淋巴结转移者（p＜0.05）。病理分期为Ⅰ-Ⅱ期患者的p33ING1和Beclin1的mRNA或蛋白表达高于Ⅲ-Ⅳ期患者（p＜0.05）。但NSCLC组织中突变型p53蛋白表达显著高于周围非癌组织（p＜0.05）。高分化和中分化NSCLC组织中突变型p53蛋白表达高于低分化NSCLC组织（p＜0.05）。有淋巴结转移的NSCLC组织中突变型p53蛋白表达高于无淋巴结转移者（p＜0.05）。病理分期为Ⅰ-Ⅱ期患者的突变型p53蛋白表达低于Ⅲ-Ⅳ期患者（p＜0.05）。p33ING1、p53及自噬相关Beclin1基因的这些表达变化与NSCLC的肿瘤细胞分化、淋巴结转移及病理分期相关，但这三个基因的表达变化与性别、年龄、原发癌大小、NSCLC组织学类型无关（p＞0.05）。NSCLC组织中p53和Beclin1的mRNA表达与p33ING1 mRNA表达相关（p＜0.05）。生长抑制、自噬及凋亡的活性变化可能与NSCLC的发生发展有关。联合检测p33ING1、p53及Beclin1基因和蛋白将有助于NSCLC的早期诊断和预后判断，并可为NSCLC的生物治疗提供实验依据。
