Li Zhenling, Zhang Yue, Jin Tiefeng, Men Jiguang, Lin Zhenhua, Qi Peng, Piao Yingshi, Yan Guanghai
Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China.
Department of TCM, Jilin Cancer Hospital, Changchun, 130012, China.
BMC Cancer. 2015 Mar 31;15:207. doi: 10.1186/s12885-015-1227-8.
High-level expression of
NAD(P)H: quinoneoxidoreductase 1 (NQO1) has been correlated with many types of human cancers, suggesting that NQO1 plays important roles in tumor occurrence and progression. This study attempted to explore the role of NQO1 in tumor progression and prognostic evaluation of non-small cell lung cancer (NSCLC).
Total 164 tissue samples, including 150 NSCLC paired with the adjacent non-tumor tissues and 14 normal lung tissues, were picked-up for immunohistochemical (IHC) staining of the NQO1 protein, and immunofluorescence (IF) staining was also performed to detect the subcellular localization of the NQO1 protein in A549 human lung cancer cells. The correlation between NQO1 expression and clinicopathological characteristics were evaluated by Chi-square test and Fisher's exact tests. The disease-free survival (DFS) and overall survival (OS) rates of NSCLC patients were calculated by the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model.
The NQO1 protein showed a mainly cytoplasmic staining pattern in lung cancer cells, including adenocarcinoma and squamous cell carcinoma (SCC). Both positive rate and strongly positive rate of NQO1 protein expression were significantly higher in NSCLC (59.3% and 28.0%) than that in adjacent non tumor (8.0% and 1.3%) and normal lung tissues (0%). The positive rate of NQO1 was related with clinical stage and lymph node metastasis, and the strongly positive rate of NQO1 protein was significantly correlated with tumor size, poor differentiation, advanced clinical stage and lymph node metastasis in NSCLC. Additionally, survival analyses showed that the patients with NQO1 positive expression had lower OS rates compared with those with NQO1 negative expression in the groups of T1-2, T3-4, without LN metastasis and stage I-II of NSCLC, respectively; however, in the groups of patients with LN metastasis or III-IV stages, OS rate was not correlated with NQO1 expression status. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with tumor size, differentiation, lymph node metastasis and clinical stage in patients with NSCLC.
NQO1 is upregulated in NSCLC, and it may be a useful poor prognostic biomarker and a potential therapeutic target for patients with NSCLC.
NAD(P)H：醌氧化还原酶1（NQO1）的高水平表达与多种人类癌症相关，提示NQO1在肿瘤发生和进展中起重要作用。本研究旨在探讨NQO1在非小细胞肺癌（NSCLC）肿瘤进展及预后评估中的作用。
选取164份组织样本，包括150例NSCLC及其配对的癌旁非肿瘤组织和14例正常肺组织，进行NQO1蛋白的免疫组织化学（IHC）染色，并进行免疫荧光（IF）染色以检测NQO1蛋白在A549人肺癌细胞中的亚细胞定位。采用卡方检验和Fisher确切概率法评估NQO1表达与临床病理特征之间的相关性。采用Kaplan-Meier法计算NSCLC患者的无病生存期（DFS）和总生存期（OS），并使用Cox比例风险回归模型进行单因素和多因素分析。
NQO1蛋白在肺癌细胞中呈主要的细胞质染色模式，包括腺癌和鳞状细胞癌（SCC）。NSCLC中NQO1蛋白表达的阳性率（59.3%）和强阳性率（28.0%）显著高于癌旁非肿瘤组织（8.0%和1.3%）和正常肺组织（0%）。NQO1的阳性率与临床分期和淋巴结转移相关，NQO1蛋白的强阳性率与NSCLC的肿瘤大小、低分化、临床晚期和淋巴结转移显著相关。此外，生存分析显示，在NSCLC的T1-2、T3-4、无淋巴结转移和I-II期组中，NQO1阳性表达患者的OS率分别低于NQO1阴性表达患者；然而，在有淋巴结转移或III-IV期患者组中，OS率与NQO1表达状态无关。此外，多因素分析表明，NQO1与肿瘤大小、分化程度、淋巴结转移和临床分期一起，成为NSCLC患者显著的独立预后因素。
NQO1在NSCLC中上调，它可能是NSCLC患者有用的不良预后生物标志物和潜在的治疗靶点。
