叉头框转录因子O1和Kruppel样转录因子9在非小细胞肺癌中的表达及其临床意义

Expressions of forkhead transcription factor O1 and Kruppel like transcription factor 9 in non-small cell lung cancer and their clinical significances

目的探讨非小细胞肺癌(NSCLC)组织中叉头框转录因子O1(FOXO1)与Kruppel样转录因子9(KLF9)的表达及其临床意义。方法收集2012年9月至2015年6月榆林市第一医院手术切除的102例NSCLC肿瘤组织标本,另选取距癌组织边缘≥5 cm的癌旁组织作为对照组。采用实时定量聚合酶链反应(qRT-PCR)检测NSCLC组织及癌旁组织中FOXO1与KLF9 mRNA相对表达量,免疫组织化学法检测NSCLC组织及癌旁组织中FOXO1、KLF9蛋白表达。根据癌组织mRNA检测结果的均值将FOXO1、KLF9分为高表达组与低表达组,分析二者与患者临床病理参数的关系。采用Pearson法对FOXO1、KLF9的表达进行相关性分析,采用Kaplan-Meier法对患者生存情况进行分析,对影响NSCLC预后的相关因素进行logistic回归分析。结果与癌旁组织相比,NSCLC组织FOXO1 mRNA相对表达量升高(2.82±0.15比1.28±0.47,t=31.525,P<0.05),KLF9 mRNA相对表达量降低(0.34±0.07比1.04±0.11,t=54.222,P<0.05)。FOXO1在有淋巴结转移、分化程度高、TNM分期为Ⅲ~Ⅳ期患者癌组织中的表达水平较高,差异均有统计学意义(均P<0.05);KLF9在有淋巴结转移、分化程度高、TNM分期为Ⅲ~Ⅳ期患者癌组织中的表达水平较低,差异均有统计学意义(均P<0.05)。Pearson相关分析法显示FOXO1与KLF9表达无相关性(r=0.154,P=0.156)。Kaplan-Meier法分析结果显示FOXO1高表达组3年总生存率低于FOXO1低表达组(10.81%比60.71%,χ^2=27.341,P<0.01),KLF9低表达组3年总生存率低于KLF9高表达组(26.32%比61.54%,χ^2=8.526,P=0.003)。logistic回归分析结果显示FOXO1高表达是影响NSCLC预后的危险因素(OR=2.682,P=0.003),KLF9高表达是NSCLC预后的保护因素(OR=0.446,P=0.012)。结论NSCLC组织中FOXO1高表达与KLF9低表达可作为预测NSCLC进展情况的有效指标,二者均与患者预后不良密切相关。

Objective To investigate the expressions of forkhead transcription factor O1 (FOXO1) and Kruppel like transcription factor 9 (KLF9) in non-small cell lung cancer (NSCLC) and their clinical significances. Methods A total of 102 patients with NSCLC who underwent surgical resection in the First Hospital of Yulin from September 2012 to June 2015 were selected as NSCLC group, and the paracancerous tissues more than 5 cm far from the edge of the cancer tissues were selected as the control group. The relative expressions of FOXO1 and KLF9 mRNA in NSCLC tissues and paracancerous tissues were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and the immunohistochemistry was used to detect the expressions of FOXO1 and KLF9 in NSCLC tissues and paracancerous tissues. According to the mean mRNA expression in NSCLC tissues, FOXO1 and KLF9 were divided into high expression group and low expression group, their relationships with clinicopathological parameters were observed. The correlation of FOXO1 and KLF9 expressions was analyzed by Pearson method, and the survival of patients was analyzed by Kaplan-Meier method, logistic regression analysis was performed on the related factors affecting the prognosis of NSCLC. Results Compared with the control group, the expression level of FOXO1 in NSCLC group increased (1.28±0.47 vs. 2.82±0.15, t= 31.525, P < 0.05), while the expression level of KLF9 decreased (1.04±0.11 vs. 0.34±0.07, t= 54.222, P < 0.05). The expressions of FOXO1 were lower in NSCLC tissues of patients with lymph node metastasis, high differentiation, and TNM stage Ⅲ-Ⅳ than those in NSCLC tissues of patients without lymph node metastasis, middle and low differentiation, and TNM stage Ⅰ-Ⅱ, and the differences were statistically significant (all P < 0.05). The expressions of KLF9 were higher in NSCLC tissues of patients with lymph node metastasis, high differentiation, and TNM stage Ⅲ-Ⅳ than those in NSCLC tissues of patients without lymph node metastasis, middle and low differentiation and TNM stage Ⅰ-Ⅱ, and the differences were statistically significant (all P < 0.05). Pearson correlation analysis showed that there was no significant correlation between FOXO1 and KLF9 expression (r= 0.154, P= 0.156). Kaplan-Meier analysis showed that the 3-year overall survival rate of FOXO1 high expression group was lower than that of FOXO1 low expression group (10.81% vs. 60.71%,χ^2= 27.341, P < 0.01). The 3-year overall survival rate of KLF9 low expression group was lower than that of KLF9 high expression group (26.32% vs. 61.54%,χ^2= 8.526, P= 0.003). Logistic regression analysis showed that FOXO1 was a risk factor for the prognosis of NSCLC (OR= 2.682, P= 0.003), and KLF9 was a protective factor for the prognosis of NSCLC (OR= 0.446, P= 0.012). Conclusions The high expression of FOXO1 and the low expression of KLF9 in NSCLC tissues can be used as effective indexes to predict the progression of NSCLC. The expressions of FOXO1 and KLF9 are closely related to the poor prognosis of patients.