Genetic Fingerprint Concerned with Lymphatic Metastasis of Human Lung Squamous Cancer

背景与目的筛选肺鳞癌患者淋巴转移差异表达基因群。方法原发癌组织及区域淋巴结取自10例接受完全性肺癌切除手术的肺鳞癌患者。根据组织来源将标本分为三组:不伴淋巴转移的肺鳞癌组织(TxN-,n=5)、伴有淋巴转移的肺鳞癌组织(TxN+,n=5)及相应转移淋巴结中的肺鳞癌细胞(N+,n=5)。对各组进行激光显微切割以获得纯净癌细胞,T7RNA线性扩增获取足够量的RNA,实验通道和参照通道分别标记以后与含6000个已知人类基因或表达序列标签的cDNA基因芯片杂交,扫描荧光信号以后进行数据分析。结果共有37个基因可将TxN+组与TxN-组区分开,其中在TxN+组高表达的基因有8个,主要涉及蛋白合成、信号传导、伴侣蛋白和酶等。有29个基因在TxN-组高表达,这些基因主要编码细胞周期调节子、转导子、信号传导蛋白以及细胞凋亡调节蛋白。比较N+组与TxN+组却没有发现具有显著性的差异表达基因。结论肺鳞癌的淋巴转移表型的获得可能是早期事件。这些差异基因的发现有助于阐明肺鳞癌淋巴转移的分子机制和寻找新的治疗靶点。

Identification of key genes and biological pathways in lung adenocarcinoma by integrated bioinformatics analysis

BACKGROUND The objectives of this study were to identify hub genes and biological pathways involved in lung adenocarcinoma(LUAD)via bioinformatics analysis,and investigate potential therapeutic targets.AIM To determine reliable prognostic biomarkers for early diagnosis and treatment of LUAD.METHODS To identify potential therapeutic targets for LUAD,two microarray datasets derived from the Gene Expression Omnibus(GEO)database were analyzed,GSE3116959 and GSE118370.Differentially expressed genes(DEGs)in LUAD and normal tissues were identified using the GEO2R tool.The Hiplot database was then used to generate a volcanic map of the DEGs.Weighted gene co-expression network analysis was conducted to cluster the genes in GSE116959 and GSE-118370 into different modules,and identify immune genes shared between them.A protein-protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes database,then the CytoNCA and CytoHubba components of Cytoscape software were used to visualize the genes.Hub genes with high scores and co-expression were identified,and the Database for Annotation,Visualization and Integrated Discovery was used to perform enrichment analysis of these genes.The diagnostic and prognostic values of the hub genes were calculated using receiver operating characteristic curves and Kaplan-Meier survival analysis,and gene-set enrichment analysis was conducted.The University of Alabama at Birmingham Cancer data analysis portal was used to analyze relationships between the hub genes and normal specimens,as well as their expression during tumor progression.Lastly,validation of protein expression was conducted on the identified hub genes via the Human Protein Atlas database.RESULTS Three hub genes with high connectivity were identified;cellular retinoic acid binding protein 2(CRABP2),matrix metallopeptidase 12(MMP12),and DNA topoisomerase II alpha(TOP2A).High expression of these genes was associated with a poor LUAD prognosis,and the genes exhibited high diagnostic value.CONCLUSION Expression levels of CRABP2,MMP12,and TOP2A in LUAD were higher than those in normal lung tissue.This observation has diagnostic value,and is linked to poor LUAD prognosis.These genes may be biomarkers and therapeutic targets in LUAD,but further research is warranted to investigate their usefulness in these respects.

Altered gene expression profiles of NIH3T3 cells regulated by human lung cancer associated gene CT120

CT120, a novel membrane-associated gene implicated in lung carcinogenesis, was previously identified from chromosome 17p13.3 locus, a hot mutation spot involved in human malignancies. In the present study, we further determined that CT120 ectopic expression could promote cell proliferation activity of NIH3T3 cells using MTS assay, and monitored the downstream effects of CT120 in NIH3T3 cells with Atlas mouse cDNA expression arrays. Among 588 known genes, 133 genes were found to be upregulated or downregulated by CT120. Two major signaling pathways involved in cell proliferation, cell survival and anti-apoptosis were overexpressed and activated in response to CT120: One is the Raf/MEK/Erk signal cascades and the other is the PI3K/Akt signal cascades, suggesting that CT120 might contribute, at least in part, to the constitutively activation of Erk and Akt in human lung caner cells. In addition, some tumor metastasis associated genes cathepsin B, cathepsin D, cathepsin L, MMP-2/TIMP-2 were also upregulated by CT120, upon which CT120 might be involved in tumor invasiveness and metastasis. In addition, CT120 might play an important role in tumor progression through modulating the expression of some candidate 'Lung Tumor Progression' genes including B-Raf, Rab-2, BAX, BAG-1, YB-1, and Cdc42.

A need for stratification of metastasis samples according to secondary site in gene expression studies

Comparisons of gene expression profiles between primary tumors and metastasis have revealed genes that are implicated in metastasis formation.However,gene expression studies conducted on metastasis samples from the same primary site usually do not discriminate between different secondary sites.Although the change in the expression of number of genes is expected to be common to metastasis from the same primary but different secondary sites,herein the data that point to substantial differences are presented.Furthermore,the reciprocal communication between metastatic and host cells that is influencing these differences is outlined to emphasize the need for stratification of metastasis samples in gene expression studies.

The Difference of Gene Expression Prof ile in Human Large Cell Lung Cancer Cell Lines with Different Metastatic Potential

Background and Objective Lung cancer is the most lethal malignangy that threatens human heath and lives nowadays in the world, and meanwhile is also the one with worst

5-mRNA-based prognostic signature of survival in lung adenocarcinoma

BACKGROUND Lung adenocarcinoma(LUAD)is the most common non-small-cell lung cancer,with a high incidence and a poor prognosis.AIM To construct effective predictive models to evaluate the prognosis of LUAD patients.METHODS In this study,we thoroughly mined LUAD genomic data from the Gene Expression Omnibus(GEO)(GSE43458,GSE32863,and GSE27262)and the Cancer Genome Atlas(TCGA)datasets,including 698 LUAD and 172 healthy(or adjacent normal)lung tissue samples.Univariate regression and LASSO regression analyses were used to screen differentially expressed genes(DEGs)related to patient prognosis,and multivariate Cox regression analysis was applied to establish the risk score equation and construct the survival prognosis model.Receiver operating characteristic curve and Kaplan-Meier survival analyses with clinically independent prognostic parameters were performed to verify the predictive power of the model and further establish a prognostic nomogram.RESULTS A total of 380 DEGs were identified in LUAD tissues through GEO and TCGA datasets,and 5 DEGs(TCN1,CENPF,MAOB,CRTAC1 and PLEK2)were screened out by multivariate Cox regression analysis,indicating that the prognostic risk model could be used as an independent prognostic factor(Hazard ratio=1.520,P<0.001).Internal and external validation of the model confirmed that the prediction model had good sensitivity and specificity(Area under the curve=0.754,0.737).Combining genetic models and clinical prognostic factors,nomograms can also predict overall survival more effectively.CONCLUSION A 5-mRNA-based model was constructed to predict the prognosis of lung adenocarcinoma,which may provide clinicians with reliable prognostic assessment tools and help clinical treatment decisions.

Selective gene therapy for human lung adenocarcinoma by tumor-specific expression of herpes simplex virus thymidine kinase gene

According to the fact that CEA gene expressed only in lung adenocarcinoma but not in normal lung cells, a retroviral expression vector (pCEATK) of the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by CEA promoter was constructed and introduced into CEA-producing human lung adenocarcinoma cells GL and non-CEA-producing HeLa cells. The expression of pCEATK and Ganciclovir (GCV) sensitivity of the transfected cells were tested in vitro and in vivo . pCEATK expressed only in CEA-producing GL cells but not in non-CEA-producing HeLa cells. The sensitivity to GCV of pCEATK-transfected GL was 992 times higher compared with that of the parental cell line and there was obvious 'bystander effect' in vitro. HeLa cells transfected wtih pCEATK were still resistant to GCV. Injection of GCV resulted in significant regression of pCEATK-transfected GL tumors in nude mice. In addition, all mice with any fraction of GL cells expressing HSV-TK exhibited a significant reduction in tumor growth, including mice with only 10% of GL cells expressing HSV-TK. These results show the possibility of HSV-TK gene-drug therapy using the tumor-specific promoter of CEA gene against CEA-producing lung cancers which was usually refractory to conventional chemotherapy.

Identification of potential immune-related prognostic biomarkers of lung cancer using gene co-expression network analysis

Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning,testing,and review of data.We identified KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV from a key module for validation.Results We found that the five genes were related to a poor prognosis,and the expression levels of these genes were associated with tumor stage.Furthermore,Kaplan-Meier plotter showed that the five hub genes had better prognostic values.The mean levels of methylation in lung adenocarcinoma(LUAD)were significantly lower than those in healthy lung tissues for the hub genes.However,gene set enrichment analysis(GSEA)for single hub genes showed that all of them were immune-related.Conclusion Our findings demonstrated that KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD.They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction.

The expression of c-src gene in the carcinogenesis process of human cardia adenocarcinoma

AIM To investigate the activation, expression of c src gene and its role in the carcinogenetic process of human cardia adenocarcinoma (CA). METHODS Fifty six cases of CA, 34 cases of normal, 36 cases of protiferative epithelia adjacent to carcinoma, and 20 cases of lymph node metastases of CA were studied for PP60 c src , the expression product of c src gene immunohistochemically by using the specific monoclonal antibody, Mab327. RESULTS The positive rates of PP60 c src in the normal epithelia, protiferative epithelia, CA and lymph node metastases were 29 4% (10/*!34), 94 4% (34/*!36), 71 4% (40/*!56) and 60 0% (12/*!20) , respectively, among them, the differences of the positive rates were statistically significant ( P <0 01) . The expression levels of PP60 c src in CA and proliferative epithelia were significantly higher than that in the normal epithelia ( P <0 01) . The PP60 c src positive rates in the papillary, tubular, poorly differentiated and mucous adenocarcinoma were 75 0% (6/*!8) , 81 8% (18/*!22) , 50 0% (10/*!20) and 100 0% (6/*!6) , respectively, whereas those of tubular and mucous adenocarcinomas were significantly higher than those of papillary and poorly differentiated adenocarcinomas ( P <0 05) , and the PP60 c src expression levels of tubular and mucous adenocarcinomas were also significantly higher than those of papillary and poorly differentiated adenocarcinomas ( P <0 01) . CONCLUSION The activation and expression of c src gene are associated with the initiation and development of human CA; the protein amount of PP60 c src increased during the process of carcinogenesis; and PP60 c src expression is also related to lymph node metastases.

Expression Profile of Metastasis-associated Genes in Esophageal Squamous Cell Carcinoma

The differentially expressed genes between esophageal squamous cell carcinoma （ESCC） with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 （4. 85 %） genes significantly differed between the ESCC with and without lymphatic metastasis （P〈0.05）, of which 18（2.03 %）were upregulated and 25 （2.82 %） down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.

Key Role of CD151-integrin Complex in Lung Cancer Metastasis and Mechanisms Involved

Tetraspanin CD151 was found to be upregulated in malignant cell types and has been identified as a tumor metastasis promoter.In this study,we aimed to examine the role of the CD151-integrin complex in lung cancer metastasis and the underlying mechanisms.CD151 QRD194–196→AAA194–196 mutant was generated and used to transfect A549 human lung adenocarcinoma cells.We found that there was no significant difference in CD151 protein expression between CD151 and CD151-AAA mutant groups.In vitro,CD151-AAA mutant delivery abrogated the migration and invasion of A549 cells,which was promoted by CD151 gene transfer.Furthermore,CD151-AAA delivery failed to activate FAK and p130Cas signaling pathways.Western blot and immunohistochemical staining showed strong CD151 expression in lung cancerous tissues but not in adjacent normal tissues.Increased level of CD151 protein was observed in 20 of the patients and the positive rate of CD151 protein in specimens was 62.5%(20/32).In addition,CD151 was co-localized withα3 integrin at the cell-cell contact site in carcinoma tissues.These results suggested that the disruption of the CD151-α3 integrin complex may impair the metastasis-promoting effects and signaling events induced by CD151 in lung cancer.Our findings identified a key role for CD151-α3 integrin complex as a promoter in the lung cancer.

Influence of Nm23-H1 Gene Site Mutagenesis on Invasive And Metastatic Phenotype in Human High-Metastatic Large Cell Lung Cancer Cell Line L9981

Background and Objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. To study and elucidate the molecular mechanism

Expression of bcl-2 protein in gastric carcinoma and its significance

AIM To further study the role of bcl 2 protein expression in gastric carcinogenesis and tumor progression. METHODS Using immunohistochemical staining, the bcl 2 protein expression in 50 cases of gastric carcinoma and its relation to clinical status and pathomorphological parameters were observed. RESULTS Forty one (82%) cases were positive for bcl 2 protein staining which was located in the cytoplasm and nuclear membrane of tumor cells. The rate of bcl 2 protein expression was not correlated with the patient, sex, tumor size, lymph node status or clinical stages ( P >0 05). It was strongly associated with intestinal type tumors and poorly differentiated tumors ( P <0 05 and P <0 01). CONCLUSION Aberrant bcl 2 protein expression appears to be specifically associated with development of intestinal type gastric carcinoma, bcl 2 protein expression might play an important role in the early development/promotion and phenotypic differentiation of gastric carcinomas, but not in tumor progression.

早期多原发与单发肺腺癌结节的临床特征及淋巴结转移风险对比

目的探讨多原发肺腺癌结节与单发肺腺癌结节的临床特征和淋巴结转移风险差异。方法回顾分析南方医科大学珠江医院胸外科于2022~2023年收治的手术患者212例,其中单发肺腺癌结节(149例)和多原发肺腺癌结节(63例),经倾向性评分匹配后比较两组影像学特征、肿瘤血清学指标、病理免疫组化及淋巴结转移率,运用二元logistic回归探讨单发与多发对其淋巴结转移率的差异。结果经过倾向性评分匹配,两组在CT的Avr值(P=0.001)、KI-67表达水平(P<0.001)、PD-L1表达水平(P=0.002)及淋巴结转移率(P=0.030)上差异有统计学意义,但在结节类型、影像学特征(分叶征、血管集束征等)、肿瘤血清学指标(CEA、NSE等)、ALK阳性率和SYN阳性率上差异均无统计学意义。筛选有显著差异的变量(Avr、Ki-67、PD-L1),经Spearman法检验发现存在相关性。以是否发生淋巴结转移为因变量,纳入单发或多发作为分类协变量、交互纳入以上3个相关性显著的变量为自变量进行二元logistic回归分析,发现多原发腺癌结节较单发腺癌结节发生淋巴结转移的概率低80.8%(RR=0.192,P=0.042)。结论多原发腺癌结节较单发腺癌结节生物学行为较温和,发生淋巴结转移的概率较低;对于多原发肺腺癌结节,应基于术中冰冻病理及影像学等综合评估,制定个性化的治疗方案。

肺腺癌差异表达基因及其对患者生存预后的影响分析

目的基于GEPIA数据库探讨正常组织与肺腺癌组织的差异表达基因以及差异表达基因与肺腺癌分期的关系,Kaplan-Meier Plotter数据库分析该基因对肺腺癌患者生存预后的影响和TIMER数据库分析差异表达基因与肿瘤免疫细胞浸润的关系。方法通过使用GEPIA数据库来获得正常组织和肺腺癌的差异表达基因以及获取差异表达基因与肺腺癌分期的关系,通过使用Kaplan-Meier Plotter数据库对这些基因进行生存预后分析和通过使用TIMER数据库对差异表达基因进行肿瘤免疫细胞浸润分析;使用实时荧光定量PCR(qRT-PCR)验证FAM83A在肺腺癌细胞中的表达水平。结果在GEPIA中,肺腺癌差异表达基因前10位分别为:RP11-40C6.2、XAGE1A、XAGE1B、RP5-940J5.9、IGHGP、CRABP2、FAM83A、SPP1、TMPRSS4、CEACAM5,均在肺腺癌中呈高表达水平;其中IGHGP、FAM83A基因表达水平与肺腺癌分期相关,而RP11-40C6.2、XAGE1A、XAGE1B、RP5-940J5.9、CRABP2、SPP1、TMPRSS4、CEACAM5基因表达水平与肺腺癌分期无显著相关;在Kaplan-Meier Plotter生存分析中,XAGE1A、XAGE1B、CRABP2、FAM83A、SPP1、TMPRSS4表达水平与OS呈负相关;XAGE1A、XAGE1B、CRABP2、FAM83A、SPP1表达水平与FP呈负相关;FAM83A表达水平与PPS呈负相关。在TIMER免疫细胞浸润分析中,CRABP2与CD4+T细胞、巨噬细胞、中性粒细胞、树突状细胞呈正相关,与肿瘤纯度呈负相关;FAM83A与B细胞、树突状细胞呈负相关;SPP1与巨噬细胞、中性粒细胞、树突状细胞呈正相关,与肿瘤纯度呈负相关;TMPRSS4与CD4+T细胞呈正相关,与CD8+T细胞呈负相关;CEACAM5与CD4+T细胞呈正相关,与CD8+T细胞呈负相关。qRT-PCR实验结果显示,FAM83A在肺腺癌细胞中呈高表达水平,差异具有统计学意义(P<0.05)。结论肺腺癌组织与正常组织之间存在差异表达基因,其中FAM83A在肺腺癌细胞中呈高表达水平,与肺腺癌患者分期、免疫细胞浸润、预后不良相关,可能是预测生存预后的一个潜在生物标志物。

基于Lasso-Cox回归模型的肺腺癌基因学预后风险分析

目的通过构建Lasso-Cox模型筛选肺腺癌差异表达基因,计算患者风险评分,构建肺腺癌预测模型,为肺腺癌的研究提供潜在的基因靶点,并为临床诊疗及预后提供新方向。方法下载癌症基因组图谱(TCGA)和肿瘤基因表达数据库(GEO)的肺腺癌基因表达和临床数据,用TCGA数据库训练模型,并合并两数据库用以模型验证,筛选的肺腺癌差异表达基因(DEGs)通过多因素Lasso-Cox回归构建风险评分预后模型,结合临床资料以确定肺腺癌最终的独立预后预测因素。利用GO富集分析、KEGG通路分析和CIBERSORTx免疫分析对风险模型差异表达基因进行生物学解释。结果通过单变量Cox和Lasso-Cox回归分析,获得了与肺腺癌预后相关的9个差异表达基因。结合临床数据的多因素Cox回归模型显示,恶性肿瘤病史、N分期、T分期和风险评分是预后的独立影响因素。结论本研究构建的肺腺癌预后模型可以有效预测患者的预后风险,为临床决策和个性化治疗提供理论基础。

hsa-miR-1293正向调控双硫死亡基因SLC3A2促进肺腺癌发展

目的 通过生物信息学方法对肺腺癌患者的基因表达谱芯片进行分析,研究影响肺腺癌的发展机制,探索肺腺癌新的治疗靶点。方法 从癌症基因图谱数据库下载mRNA和miRNA表达数据,通过R语言和生存分析筛选关键基因并通过数据库生存模块进行验证,对预后相关基因进行高表达通路富集分析。最后进行关键基因与免疫细胞相关性分析。结果 经筛选确定关键双硫死亡基因SLC3A2和关键核激活miRNA(hsa-miR-1293),SLC3A2与hsa-miR-1293表达呈正相关,其表达越高,肺腺癌患者预后越差。与SLC3A2最显著相关的富集通路为氨酰基转移RNA生物合成。SLC3A2与4种差异免疫细胞呈正相关,与4种差异免疫细胞呈负相关。结论 hsa-miR-1293正向调控双硫死亡基因SLC3A2表达促进肺腺癌的发生发展,可为肺腺癌开发新的治疗靶点提供思路。

基于生物信息学对肺腺癌核心基因的预测及验证

目的:基于生物信息学对肺腺癌核心基因进行预测及验证。方法:采用GEO数据库收集肺腺癌数据集,采用R软件处理,收集36例肺腺癌患者的肿瘤组织样本及邻近正常肺组织样本并验证表达水平。结果:差异表达基因主要富集于卷曲结合、糖胺聚糖结合、肝素结合和细胞外基质结构成分,Wnt信号通路、ecm-受体相互作用、肿瘤蛋白多糖三条通路与之密切相关。7个核心基因中,5个基因的表达水平具有统计学意义,分别是PPBP、ADRA1B、CDCA8、CENPA和NMUR1。结论:PPBP、ADRA1B、CDCA8、CENPA和NMUR1基因可能是肺腺癌潜在生物标志物。

CD44 v6基因编码蛋白表达与胃癌转移和预后的关系

目的观察转移相关粘附分子拼接变异体ＣＤ４４ｖ６在人胃癌组织中的不同表达，探讨ＣＤ４４ｖ６与胃癌病理生物学行为之间的关系，评价ＣＤ４４ｖ６可否作为一个新的客观预测胃癌细胞转移潜能和胃癌患者预后的可靠生物学指标．方法采用鼠抗人ＣＤ４４ｖ６特异性ｍＡｂ，对４５例早期胃癌，２２例中期胃癌和１０３例晚期胃癌手术切除标本之胃原发灶与转移灶进行了ＡＢＣ免疫组化检测．应用χ２检验和Ｌｏｇｒａｎｋ检验方法对结果做统计学分析．结果ＣＤ４４ｖ６在晚期胃癌中的检出率为４６６％（４８／１０３），明显高于早期胃癌（２６７％，１２／４５）和中期胃癌（２７３％，６／２２，Ｐ＜００１）．伴淋巴结转移和伴肝脏转移之胃癌ＣＤ４４ｖ６检出率分别为４９％（５０／１０２）和７１４％（５／７），明显高于不伴转移的胃癌（１８６％，１１／５９，Ｐ＜００１）．肠型胃癌中ＣＤ４４ｖ６检出率为４４９％（４８／１０７），明显高于弥漫型胃癌（２７４％，１７／６２，Ｐ＜００５）．但是，ＣＤ４４ｖ６的表达与胃癌原发灶大小和组织学类型及分化程度未见明显相关．ＣＤ４４ｖ６阳性胃癌患者的术后生存期显著短于ＣＤ４４ｖ６阴性胃癌的患者（Ｐ＝００００２）．结论?

肺腺癌患者淋巴转移的分子指纹鉴定

背景与目的:远处转移是肺癌患者的重要死因,癌转移可能与细胞内基因表达模式改变有关。急需运用新技术来筛选和分析这些基因,以便进一步阐明癌转移的机制并寻找新的治疗靶点。本研究旨在筛选肺腺癌患者淋巴转移差异表达基因。方法:原发癌组织及区域淋巴结取自22例接受根治性手术的肺腺癌患者。根据组织来源将标本分为三组:不伴淋巴转移的肺腺癌组织(TxN-,n=11)、伴有淋巴转移的肺腺癌组织(TxN+,n=11)及相应转移淋巴结中的肺腺癌细胞(N+,n=11)。对各组进行激光显微切割以获得纯净癌细胞,T7RNA线性扩增获取足够量的RNA,实验通道和参照通道分别标记以后与含6000个已知人类基因或表达序列标签的cDNA基因芯片杂交,扫描荧光信号以后进行数据分析。结果:TxN+组与TxN-组共有17个差异表达基因,其中12个基因表达上调,5个基因表达下调。有53个基因可将N+组与TxN+组区分开,其中在N+组高表达的基因有25个,在TxN+组高表达的有28个。结论:早期癌形成中的遗传学变化和后期癌进展中的获得性分子学变异共同决定肺腺癌的淋巴转移。