Bufalin inhibits epithelial-mesenchymal transition and increases radiosensitivity of non-small cell lung cancer via inhibition of the Src signaling

BackgroundEpithelial-mesenchymal transition (EMT) is a biological process involved in tumor migration, invasion, and radiotherapy resistance. Bufalin can affect the proliferation, apoptosis and invasion of tumor cells by regulating multiple signaling pathways. Whether bufalin can increase radiosensitivity through EMT deserves further investigation.MethodsIn this study, we investigated the effect of bufalin on the EMT and radiosensitivity of non-small cell lung cancer (NSCLC) and the underlying molecular mechanism. NSCLC cells were treated with bufalin (at a dose of 0–100 nM) or irradiated with 6 MV X-rays (4 Gy/min). The effects of bufalin on cell survival, cell cycle, radiosensitivity, cell migration, and invasion were detected. Western blot was used to analyze the gene expression changes of Src signaling in NSCLC cell induced by Bufalin.ResultsBufalin significantly inhibited cell survival, migration, and invasion and induced G2/M arrest and apoptosis. Cells co-treated with bufalin and radiation manifested a higher inhibitory effect compared to those treated with radiation or bufalin alone. Furthermore, the levels of p-Src and p-STAT3 were considerably reduced following bufalin treatment. Interestingly, elevated p-Src and p-STAT3 were observed in cells treated with radiation. Bufalin inhibited radiation-induced p-Src and p-STAT3, whereas the knockdown of Src abrogated the effects of bufalin on cell migration, invasion, EMT, and radiosensitivity.ConclusionsBufalin inhibits EMT and enhances radiosensitivity through targeting Src signaling in NSCLC.     

Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.Proteasomes are multisubunit complexes that degrade intracellular proteins through the ubiquitin–proteasome pathway (1). The three catalytic β subunits β1, β2, and β5 in the proteasome complex are replaced by proteasome (prosome, macropain) subunit B9 (PSMB9)/β1i, PSMB10/β2i, and PSMB8/β5i, respectively, to form the immunoproteasome (2). The immunoproteasome generates peptides suitable for binding onto HLA I molecules, facilitating antigen presentation for CD8⁺ T-cell responses. Lack of expression or down-regulation of the immunoproteasome may contribute to immune evasion through antigen loss (3).The impact of immunoproteasome expression on antigen presentation in tumors of epithelial origin is not well established. We have investigated the constitutive and induced expression patterns of immunoproteasome subunits in non-small cell lung carcinoma (NSCLC) and their impact on antigen presentation. We provide evidence for dysregulated expression of immunoproteasome subunits in NSCLC cells with a mesenchymal phenotype, associated with a markedly reduced repertoire of HLA-bound peptides. Reduced expression of immunoproteasome subunits in NSCLC was also associated with reduced disease free survival.     

非小细胞肺癌中 ALDH1 和 ABCG2 的表达及其临床意义简

目的 检测ALDH1和ABCG2在人非小细胞肺癌组织中的表达状况,探讨二者的相关性及其与临床病理特征的关系.方法采用免疫组化 ElivisionTM plus法检测60例NSCLC和30例癌旁正常肺组织中ALDH1、ABCG2的表达情况.结果 在癌旁正常肺组织中ALDH1、ABCG2的表达率分别为10%、0%,在NSCLC 组织中分别为63.3%、48.3%,差异有显著（P＜0.05）;其阳性表达与肿瘤细胞分化程度、临床分期、淋巴结转移（P均＜ 0.05）; ALDH1的表达与ABCG2的表达无明显相关（P＞0.05）.结论 ALDH1、ABCG2的表达在NSCLC的发生、发展中起重要作用,可以作为预后判断的指标.     

刚地弓形虫对荷瘤小鼠肿瘤组织微血管生成的抑制作用

摘 要：目的 观察刚地弓形虫感染对BALB/c小鼠ct26细胞皮下移植瘤血管生成的抑制作用及其作用机理。方法 建立刚地弓形虫感染的小鼠结肠癌ct26皮下移植瘤模型,观察弓形虫感染对小鼠的生存延长率、对肿瘤的质量抑制率,并采用免疫组化方法检测弓形虫感染对肿瘤组织MVD、VEGF、TSP-1表达的影响。结果 弓形虫感染的小鼠生存时间比对照组长（P<0.05）,生存延长率为57.45%,肿瘤质量抑制率为47.23%;弓形虫感染的小鼠肿瘤组织中MVD及VEGF表达水平低于对照组（P=0.005,P=0.03）,TSP-1表达高于对照组（P=0.005）。结论 弓形虫感染能抑制荷瘤小鼠肿瘤组织微血管生成;下调VEGF及上调TSP-1与弓形虫感染抗肿瘤血管生成有关。     

非小细胞肺癌碱性成纤维细胞生长因子表达与微血管密度测定的临床意义

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)表达与微血管密度(microvesseldensity,MVD)的临床意义。方法采用免疫组化SP法测定58例肺癌组织中bFGF表达和MVD,分析其与肺癌病理类型、临床分期、有无淋巴结转移的关系。结果在NSCLC中肺癌组织bFGF阳性表达率和MVD明显高于癌旁组织(P<0.01),鳞癌bFGF阳性表达率与腺癌无差异(P>0.05),但腺癌的MVD高于鳞癌(P<0.05),bFGF和MVD的表达在TNM分期之间无统计学意义,淋巴结转移阳性组bFGF和MVD的表达均明显高于淋巴结转移阴性组(P<0.01)。结论腺癌组织微血管丰富,bFGF和MVD可能与淋巴结转移有关。     

TFPI-2、VEGF在非小细胞肺癌中的表达及相关性研究

目的研究组织因子途径抑制物-2(tissue factor pathway inhibitor-2,TFPI-2)、血管内皮生长因子(vascular endotheli-al growth factor,VEGF)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其间的相关性。方法采用免疫组化法检测60例NSCLC组织TFPI-2、VEGF的表达及CD31单克隆抗体标记的微血管密度(MVD)。结果 NSCLC中临床分期为Ⅰ、Ⅱ、Ⅲ期的患者中TFPI-2表达阳性率分别为75.8%、25.0%和40.0%(P=0.003),无淋巴结转移和有淋巴结转移的患者中TF-PI-2表达阳性率分别为66.7%、38.1%(P=0.033)。临床分期为Ⅰ、Ⅱ、Ⅲ期的患者中EVGF表达阳性率分别为60.6%、88.3%和93.3%(P=0.040),无淋巴结转移和有淋巴结转移的患者中VEGF表达阳性率分别为64.1%、90.5%(P=0.028)。NSCLC组织中的TFPI-2的表达与VEGF的表达呈负相关(r=-0.351),差异有统计学意义(P=0.004)。高、低MVD组中的TFPI-2阳性表达率分别为41.2%、76.9%(P=0.006)。高、低MVD组中的VEGF阳性表达率分别为76.5%、30.87%(P=0.000)。结论 NSCLC中TFPI-2可能通过下调VEGF的表达抑制肿瘤新生血管的形成,从而抑制NSCLC的生长、浸润及转移。     

Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer

BACKGROUND AND AIM: The significance of serum levels of transforming growth factor (TGF)-beta1 in the development of gastric cancer is unclear. The purpose of this study is to determine whether serum TGF-beta1 correlated with the clinicopathological findings of patients with gastric cancer. METHODS: Transforming growth factor-beta1 levels in the serum of 275 gastric cancer patients and 275 gender- and age-matched healthy controls were measured with enzyme-linked immunosorbent assay (ELISA) using a commercially available kit. RESULTS: The mean level of serum TGF-beta1 of gastric cancer patients (15.9 +/- 5.9 ng/mL) was significantly higher than that (13.9 +/- 7.4 ng/mL) of healthy controls (P < 0.01). The odds ratio for the subjects in the highest quartile (16.7 ng/mL or more) was 4.03 (95% confidence interval, 2.14-7.58), as compared with that for the subjects in the lowest quartile (0-9.5 ng/mL). Patients with venous invasion compared to those without venous invasion had significantly elevated serum TGF-beta1 (17.3 +/- 7.2 vs 15.0 +/- 5.1 ng/mL; P = 0.04). There were no statistically significant differences between the two groups categorized by histological type, lymph node metastasis and distant metastasis. Logistical regression analysis showed that venous invasion was significantly correlated with elevated serum TGF-beta1 levels (P = 0.02). CONCLUSIONS: The present study showed that an elevated serum TGF-beta1 level may be significantly correlated with venous invasion in gastric cancer patients.     

Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis

Objective

Programmed cell death 1 (PD-1) and one of its ligands, PD-L1, are key immune checkpoint proteins. Evidences showed PD-L1 is an emerging biomarker for immunotherapy by anti-PD-1 and anti-PD-L1 antibody in non-small cell lung cancer (NSCLC). To investigate the association of PD-L1 protein expression with clinicopathological features and its impact on survival outcome, we conducted a meta-analysis.

Methods

A comprehensive literature search of electronic databases (up to July 10, 2014) was performed. Correlation between PD-L1 expression and clinicopathological features and overall survival (OS) was analyzed by synthesizing the qualified data. Publication biases were examined.

Results

A total of 1,550 NSCLC patients from 9 studies were included. The pooled odds ratios (ORs) indicated high PD-L1 expression was associated with poor tumor differentiation [OR =0.53, 95% confidence interval (CI): 0.39-0.72, P<0.0001]. Whereas, none of other clinicopathological characteristics [gender, smoking status, histological type, invasive depth of tumor, status of lymph node metastasis and tumor node metastasis (TNM) stage] were correlated with PD-L1 expression in current analysis. The combined hazard ratio (HR) for OS showed high expression of PD-L1 impaired the OS in NSCLC (HR_{positive/negative} =1.47, 95% CI: 1.19-1.83, P=0.0004).

Conclusions

Our meta-analysis indicated PD-L1 protein expression in NSCLC was not associated with common clinicopathological characteristics, except tumor differentiation. It was a poor prognostic biomarker for NSCLC. Further research should be performed to investigate the precise clinicopathological and prognostic significance of PD-L1 in NSCLC under uniform testing standard.     

PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types,tissue sampling and metastasis

BackgroundProgrammed cell death ligand-1 (PD-L1) is a predictive marker of anti-PD-1/PD-L1 therapy response. Intra-tumour heterogeneity of PD-L1 expression has been reported in non-small cell lung cancer (NSCLC), but comprehensive studies regarding the determination of PD-L1 expression in different materials are still lacking. Therefore, we aimed to compare PD-L1 expression in paired tumour samples and in different specimen types.MethodsA total of 1,002 resected NSCLC specimens, 35 biopsy specimens and 54 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples were performed PD-L1 immunohistochemistry (IHC) testing using the 22C3 assay. PD-L1 expression was evaluated using the tumour proportion score (TPS) and categorized into three levels: negative (TPS <1%), low expression (TPS 1–49%) and high expression (TPS ≥50%).ResultsA total of 1,002 resected NSCLC specimens, including 852 adenocarcinomas (ADCs) and 150 squamous cell carcinomas (SCCs); 35 paired biopsy and resected samples; 54 paired cell block and biopsy samples; 53 paired blocks from the same resected tissue and 49 paired primary and metastatic lesion samples were included in this study. Interestingly, high PD-L1 expression was significantly more frequent in poorly differentiated subtypes than in well-differentiated subtypes in the ADC subgroup (P<0.001). In the SCC subgroup, high PD-L1 expression was significantly more associated with the nonkeratinizing type than the keratinizing type (P=0.001). PD-L1 expression differed between cell blocks and matched biopsy specimens (discordance rate =11.1%, 6/54) and between biopsy and matched resected specimens (discordance rate =31.4%, 11/35). PD-L1 expression differed between different paraffin blocks from the same resected specimen (discordance rate =35.8%, 19/53), and the discordance rate of PD-L1 expression between primary tumours and matched lymph node metastases was 28.6% (14/49).ConclusionsDiscordant PD-L1 expression is not uncommon in NSCLC and warrants additional studies and serious consideration when interpreting PD-L1 test results. Initial negative test results may lead to repeat PD-L1 testing in additional samples or the use of a different clone if necessary.     

非小细胞肺癌中Survivin和Cyclin-D1的表达与细胞增殖及凋亡的相关性

目的　检测非小细胞肺癌(NSCLC)组织中Survivin和Cyclin- D1 基因的表达,探讨它们与NSCLC临床病理特征的关系。方法　应用免疫组织化学SP方法标记80例NSCLC组织(含癌旁组织和正常肺组织) ,应用TUNEL法检测癌细胞的凋亡指数。结果　在癌组织与癌旁组织及正常肺组织中survivin和cyclin- D1 表达差异有显著性(P <0 .0 1 )。在癌组织中有过表达,在癌旁组织中的表达较正常组织中的表达增强;癌组织中survivin和cyclin D1 表达呈正相关(P <0 .0 1 ) ,癌旁组织中survivin和cyclin- D1 表达也呈正相关(P <0 .0 1 )。癌组织类型、分化程度和淋巴转移与survivin和cyclin- D1 的表达均无相关性(P >0 .0 5)。不同临床分期的NSCLC ,其survivin和cyclin- D1 表达差异有显著性(P <0 .0 5)。survivin的表达评分与肿瘤的凋亡指数呈负相关(P <0 .0 5)。结论　survivin和cyclin- D1 在NSCLC的发生发展中可能起协同作用,过表达的survivin和cyclin- D1 可以作为反映NSCLC细胞分裂增殖、凋亡抑制能力和临床分期的指标之一。     

晚期非小细胞肺癌ERCC1 XRCC1基因多态性与铂类化疗疗效研究

以铂类为基础的两药化疗是晚期非小细胞肺癌(NSCLC)的主要治疗手段,有效率约为30%。然而不同个体对化疗疗效和耐受性的差异巨大。机体的损伤修复系统可以修复铂类药物引起的DNA损伤,影响化疗疗效,DNA修复基因的单核苷酸构象多态性(SNP)是导致这种差异的重要原因和分子基础,ERCC1和XRCC1分别在核苷酸切     

Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer

BackgroundA hormonal role in the development of non-small cell lung cancer (NSCLC) has been well documented, and the classic estrogen receptors (ERs)—ERα and ERβ have been extensively investigated over the past decade. The expression of ERβ was found to be high and display biological activity in NSCLC, but anti-estrogen therapy targeting this receptor has shown limited efficacy for the disease. The third estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30), was recently found to be highly expressed in NSCLC. Herein, we aimed to investigate the expression profile of GPER1 and correlate it with clinicopathological factors as well as postoperative prognosis in NSCLC.MethodsWe examined GPER1 and ERβ expression using immunohistochemistry among 183 NSCLC cases, including 132 lung adenocarcinoma (LUAD) with identified epidermal growth factor receptor (EGFR) mutation status and 51 squamous cell carcinoma (SCC) patients. We then conducted correlation analysis between the expression of GPER1 and clinicopathological factors and patients’ postoperative prognosis.ResultsPositive expression of GPER1 was categorized into 2 main classes: nuclei-GPER1 (nGPER1) and concurrent nuclei-and cytoplasm-GPER1 (n/cGPER1), according to its subcellular localization. The LUAD with wild-type EGFR (wt-EGFR) had a higher frequency of n/cGPER1 (50%) but a lower frequency of nGPER1 (31%) when compared with those with mutated EGFR (n/cGPER1: 31%, nGPER1: 41%, respectively). The expression of GPER1, regardless of subcellular localization, was positively correlated with tumor stage and lymph node metastasis. The median recurrence-free survival (mRFS) and overall survival (OS) were significantly worse in participants with n/cGPER1 expression than in those with nGPER1 or without GPER1 expression.ConclusionsThis study revealed that GPER1 is aberrantly highly expressed and presents a unique GPER1 expression profile in NSCLC. The n/cGPER1 expression was significantly associated with EGFR mutation status, tumor stage, lymph node metastasis, and poor postoperative prognosis in NSCLC.     

Clinical significance of tumor necrosis and viability in non-small cell lung cancer

BackgroundWe included tumor necrosis (TN) and tumor viability (TV) in our prognostic assessment of patients with non-small cell lung cancer (NSCLC) and investigated their clinical significance.MethodsMedical records of all consecutive subjects who underwent a lobectomy with standard mediastinal lymph node dissection for NSCLC between 2015 to 2016, were reviewed retrospectively. We analyzed the associations of TN and TV with various parameters associated with prognosis as well as survival in NSCLC patients. All analyses were performed regarding neoadjuvant therapy status [the group without neoadjuvant therapy (WON) vs. the group with neoadjuvant therapy (WN)].ResultsA consecutive 154 patients (mean age: 65.0±10.1 years) were included into the present study. Fifteen patients underwent neoadjuvant therapy. Final pathologic stages were IA1 (n=13), IA2 (n=30), IA3 (n=32), IB (n=40), IIA (n=9), IIB (n=18), and IIIA (n=12). WN significantly showed higher TN (P=0.005) and lower TV (P<0.001) than WON. Tumors with vascular, lymphatic, and perineural invasion showed significantly lower TV and higher TN than cases without these features (P=0.014, P=0.019, and P=0.012 for TV; P=0.001, P<0.001, and P<0.001 for TN, respectively). Tumors with poorer differentiation had lower TV (P<0.001) and higher TN (P<0.001) than more differentiated tumors. There was a positive correlation between TN and tumor size (P<0.001) and a negative correlation between TV and tumor size (P=0.031). TN significantly increased as pathologic stage increased (P=0.001), and TV significantly decreased as pathologic stage increased (P=0.038). The group without TN survived significantly longer than the group with TN (P=0.016) in N0 disease and presence of TN and pT stage were independent prognostic factors for survival in N0 disease (P=0.037 and P=0.021, respectively). There was a positive correlation between TN and Ki-67 level (P=0.027). In WN, TN was significantly associated with differentiation (P=0.035), tumor size (P=0.008), and pT stage (P=0.031) but not overall pathologic stage or survival.ConclusionsPresence of histological TN was associated with prognosis of NSCLC, especially in N0 disease, and its usage as a diagnostic or prognostic tool and determination of resection extent could potentially provide prognostic information that can facilitate better management of NSCLC.     

CYFRA 21-1对非小细胞肺癌胸腔积液的诊断价值

目的　探讨非小细胞肺癌标记物 (CYFRA 2 1- 1)对非小细胞肺癌 (NSCLC)胸腔积液的诊断价值。方法　用放免法测定了非小细胞肺癌 ,小细胞肺癌 (SCLC)及结核性胸膜炎的胸腔积液CYFRA 2 1- 1水平。结果　非小细胞肺癌胸腔积液的CYFRA 2 1- 1水平 ,无论细胞学阳性或阴性 ,均显著高于小细胞肺癌及结核性胸膜炎的胸腔积液组 (P <0 0 1)。结论　检测胸腔积液CYFRA 2 1- 1对非小细胞肺癌胸腔积液的诊断有重要价值     

内皮素-1与非小细胞肺癌

肺癌是一种死亡率高、危害大的疾病,严重威胁人类健康,而非小细胞肺癌占肺癌的80%以上.近年来,研究发现内皮素-1与非小细胞肺癌关系密切.非小细胞肺癌患者体内内皮素-1水平升高,通过外周血、支气管镜等检查测定内皮素-1水平,有助于非小细胞肺癌的诊断和预后的评估.     

Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer

ObjectiveTo investigate the expression of hENTl and ERCC1 genes in tumor tissues non–small cell lung cancer (NSCLC).MethodsFresh non–small lung cancer specimens were transplanted into nude mice. Twenty mice were randomized into two groups: experimental group receiving gemcitabine plus cisplatin and control group receiving 0.9% physiological saline. The expressions of hENTl and ERCC1 mRNA in tumor tissue were detected by real–time fluorescent quantitative PCR. The volume of tumor, the weight of nude mice and tumor volume were respectively measured and calculated 2–3 times per week. Tissue samples were collected from NSCLC mice treated with gemcitabine plus carboplatin.ResultsThe histological examination showed that many tumor cells were well preserved in nude mice. The rate of transplanted tumor cells was 86.7%. The concomitant treatment study showed that the rate of TV, RTV, T/C in GEM + DDP group was the lowest. LBP + DOC, DDP + DOC obviously influenced the body weight. Compared with NS group, DDP group, GEM group, the survival period and the level of hENTl of DDP+GEM group increased obviously, the level of ERCC1 decreased significantly (P<0.05).ConclusionsThe expression of hENT1 and ERCC1 genes in tumor tissues were closely correlated with the response to chemotherapy and prognosis of patients with NSCLC treated with gemcitabine plus cisplatin.     

The detection value of PD-L1 expression in biopsy specimens and surgical resection specimens in non-small cell lung cancer: a meta-analysis

BackgroundThe detection value of different types of specimens for programmed death ligand-1 (PD-L1) expression remains controversial. As such, the purpose of this meta-analysis was to compare the detection value of biopsy specimens and surgical resection specimens for PD-L1 expression in patients with non-small cell lung cancer (NSCLC).MethodsPubMed and Web of Science were searched prior to December 2020 to identify studies that compared the detection value of biopsy specimens and surgical resection specimens for PD-L1 expression in NSCLC. Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 scale was used to evaluate the quality of the literature included. The detection value of different types of specimens for PD-L1 expression was then assessed. Besides, the relative risk (RR) with 95% CI were pooled using Review Manager 5.3 software and Stata 14.0 software.ResultsThe meta-analysis involved 12 articles and included 877 patients. There was no significant difference in the detection rate of PD-L1 at the 1% cutoff between biopsy specimens and surgical resection specimens (RR =0.89, 95% CI: 0.70–1.12, P=0.33). However, there was a significant difference between two groups when the cutoff is 50% (RR =0.69, 95% CI: 0.58–0.83, P<0.01). In addition, a subgroup analysis of the type of biopsy specimens and the PD-L1 qualitative immunohistochemistry (IHC) assays showed that the detection rate of PD-L1 in small biopsies and using the SP142 antibody were lower than in surgical specimens and using other antibodies for both the 1% and 50% cut-offs (P<0.01).ConclusionsCurrent evidence suggests that caution must be taken when using biopsy specimens from patients with advanced NSCLC to evaluate PD-L1 status eligible for immunotherapy, additional biopsy specimens sampling may be needed to minimize the risk of tumor misclassification. In addition, PD-L1 qualitative IHC assays and the type of biopsy specimens related to PD-L1 expression detection.     

NDRG1在非小细胞肺癌中的表达及其与PTEN表达的相关性

目的研究NDRG1在非小细胞肺癌（NSCLC non-small cell lung cancer）中的表达、意义及其与PTEN表达的相关性。方法应用免疫组化方法检测69例NSCLC组织标本中和26例癌旁正常肺组织中NDRG1、PTEN的表达,分析NDRG1的表达与患者临床病理特征的关系及与PTEN表达的相关性。结果 NDRG1在NSCLC、癌旁正常肺组织中的阳性表达率分别为76.81%、7.69%,NSCLC中NDRG1的表达与分化程度、组织学类型、TNM分期、淋巴结转移相关（P〈0.05）,而与性别、年龄无关（P〉0.05）;NSCLC中NDRG1和PTEN表达呈负相关（rs=-0.381,P〈0.05）。结论 NSCLC中存在NDRG1的高表达,与PTEN的低表达在NSCLC的发生发展过程中共同发挥着重要的作用。