Objectives:The tumorigenic progression of Lung adenocarcinoma(LUAD),the predominant NSCLC subtype,is predominantly driven by co-occurring mutations in KRAS proto-oncogene(KRAS)/Tumor protein p53(TP53).However,their im...Objectives:The tumorigenic progression of Lung adenocarcinoma(LUAD),the predominant NSCLC subtype,is predominantly driven by co-occurring mutations in KRAS proto-oncogene(KRAS)/Tumor protein p53(TP53).However,their impact on tumor microenvironment(TME)heterogeneity,particularly neutrophil dynamics,remains poorly understood.This present study aims to elucidate how KRAS/TP53 mutations reprogram the TME and develop a neutrophil-centric prognostic signature for LUAD.Methods:Leveraging single-cell RNA sequencing data and transcriptome data,neutrophil subpopulations were identified using Seurat and CellChat R packages,with trajectory analysis via Monocle2 R package.High-dimensional weighted gene co-expression network analysis(hdWGCNA),univariate Cox regression,and least absolute shrinkage and selection operator(LASSO)regression analyses were employed to generate a prognostic signature.Functional validation included Ras homolog family member V(RHOV)knockdown in A549/H1299 cells using siRNA,were assessed by cell counting kit 8(CCK8)assay,wound healing assay,and transwell assay.Results:KRAS/TP53-mutated LUAD exhibited increased neutrophil infiltration,particularly IS MUT subtypes with enhanced OSM/CALCR/IL-1 signaling.A five-gene prognostic signature(MS4A1,ANLN,FAM83A,RHOV,KRT6A)stratified patients into high-and low-risk groups with divergent overall survival in the TCGA-LUAD cohort(p<0.0001).AUCs achieved 0.73,0.70,and 0.66 at 1-,3-,and 5-year,respectively.External validation in immunotherapy cohorts(IMvigor210,GSE78220)confirmed the fine predictive capability of the prognostic signature in predicting treatment response.An integrated prognostic nomogram combining clinicopathological features and risk score further improved its clinical utility.Pseudotime analysis found that RHOV was essential for the growth of lung epithelial cells.RHOV knockdown significantly reduced the proliferation,migration,and invasion capabilities of A549/H1299 cells in vitro.Conclusion:KRAS/TP53 mutations may drive neutrophil heterogeneity in the TME of LUAD,addressing prognostic and therapeutic value.The five-gene signature and RHOV targeting offer translational relevance for risk stratification and therapy.These findings bridge genomic alterations with TME remodeling,advancing precision oncology in LUAD.展开更多
Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was...Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.展开更多
目的:通过双向两样本MR方法探讨皮肌炎(Dermatomyositis, DM)、免疫细胞与肺癌(Lung cancer, LC)之间的因果关系,验证免疫细胞在其中起到的中介作用。方法:使用双向双样本孟德尔随机化(Mendelian Randomization, MR)法分析DM与LC及其各...目的:通过双向两样本MR方法探讨皮肌炎(Dermatomyositis, DM)、免疫细胞与肺癌(Lung cancer, LC)之间的因果关系,验证免疫细胞在其中起到的中介作用。方法:使用双向双样本孟德尔随机化(Mendelian Randomization, MR)法分析DM与LC及其各种亚型的因果关系,通过两步法MR探讨免疫细胞在DM与LC及各种亚型之间是否起到中介作用。使用MR-Egger截距法和MR-PRESSO法检查有无水平多效性,Cochran’s Q检查有无异质性。结果:根据MR分析结果,DM会增加患小细胞肺癌(Small cell lung cancer, SCLC)和肺腺癌(Lung adenocarcinoma, LUAD)的风险。38种免疫细胞表型与LC密切相关。其中,效应记忆CD8+ T细胞在CD8+ T细胞中所占的百分比、静息CD4调节性T细胞上CD25的表达水平、IgD− CD38+ B细胞的绝对计数、效应记忆CD8+ T细胞在T细胞中所占的百分比,以及CD33+ HLA-DR+ CD14低表达细胞上CD45的表达水平,都参与介导了DM与LUAD以及小细胞肺癌SCLC之间的因果关系。结论:我们的研究结果表明,DM患者并发LUAD和SCLC发生风险将显著增加。此外,我们发现五种免疫细胞性状(效应记忆CD8+ T细胞在CD8+ T细胞中所占的百分比、静息CD4调节性T细胞上CD25的表达水平、IgD− CD38+ B细胞的绝对计数、效应记忆CD8+ T细胞在T细胞中所占的百分比,以及CD33+ HLA-DR+ CD14低表达细胞上CD45的表达水平)在DM患者并发LC中的发病过程中起到重要作用。针对这些免疫细胞性状的深入研究将进一步明确DM导致LC风险升高的病理生理机制。Objective: To explore the causal relationships among dermatomyositis (DM), immune cells, and lung cancer (LC) through the bidirectional two-sample Mendelian randomization (MR) method, and to verify the mediating role of immune cells in this process. Methods: The bidirectional two-sample Mendelian randomization (MR) method was used to analyze the causal relationships between DM and LC as well as its various subtypes. The two-step MR method was applied to explore whether immune cells played a mediating role between DM and LC and its various subtypes. The MR-Egger intercept method and the MR-PRESSO method were used to check for horizontal pleiotropy, and Cochran’s Q test was used to check for heterogeneity. Results: According to the results of the MR analysis, DM increases the risk of developing small cell lung cancer (SCLC) and lung adenocarcinoma (LUAD). 38 immune cell characteristics were closely related to LC. Among them, the percentage of effector memory CD8+ T cells in CD8+ T cells, the expression level of CD25 on resting CD4 regulatory T cells, the absolute count of IgD− CD38+ B cells, the percentage of effector memory CD8+ T cells in T cells, and the expression level of CD45 on CD33+ HLA-DR+ CD14 low-expression cells all participated in mediating the causal relationships between DM and LUAD as well as SCLC. Conclusion: Our research results indicate that the risk of developing LUAD and SCLC in patients with DM will increase significantly. In addition, we found that five immune cell traits (the percentage of effector memory CD8+ T cells in CD8+ T cells, the expression level of CD25 on resting CD4 regulatory T cells, the absolute count of IgD− CD38+ B cells, the percentage of effector memory CD8+ T cells in T cells, and the expression level of CD45 on CD33+ HLA-DR+ CD14 low-expression cells) play an important role in the pathogenesis of LC in patients with DM. In-depth research on these immune cell traits will further clarify the pathophysiological mechanism by which DM leads to an increased risk of LC.展开更多
Background:Circular RNAs play an important role in regulating lung adenocarcinoma(LUAD).Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD.However,the biological mechanism of circ_0015...Background:Circular RNAs play an important role in regulating lung adenocarcinoma(LUAD).Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD.However,the biological mechanism of circ_0015278 in LUAD has not been fully clarified,especially in ferroptosis.Materials and Methods:Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278,subsequently confirmed by luciferase reporter assays.The impact of Circ_0015278 on cell proliferation,migration,invasion,and ferroptosis was investigated through a loss-of-function experiment.A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth.Results:Circ_0015278 exhibited downregulation in LUAD.It inhibited cell proliferation,migration,and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism.Moreover,circ_0015278 suppressed tumour growth in mice.Conclusions:Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD.Furthermore,it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.展开更多
Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims...Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.展开更多
目的:探讨基于CT影像组学的机器学习模型预测肺腺癌(lung adenocarcinoma,LUAD)气腔播散(spread through air spaces,STAS)的价值,并确定最佳瘤周分析区域。方法:回顾性分析2013年1月至2017年1月浙江省肿瘤医院接受非小细胞肺癌手术治疗...目的:探讨基于CT影像组学的机器学习模型预测肺腺癌(lung adenocarcinoma,LUAD)气腔播散(spread through air spaces,STAS)的价值,并确定最佳瘤周分析区域。方法:回顾性分析2013年1月至2017年1月浙江省肿瘤医院接受非小细胞肺癌手术治疗的378例LUAD患者资料,构建肿瘤边缘外扩0、3、6、9、12 mm区域的逻辑回归、随机森林和XGBoost模型。结果:6 mm区域的XGB模型在测试集上表现最佳,其次为AUC-ROC达0.855(95%CI:0.756~0.950),9 mm区域的XGB模型。DCA分析显示6 mm和9 mm区域XGB模型临床净收益较高。特征分析显示部分小波变换特征对STAS预测贡献较大。结论:本研究初步表明基于CT影像组学的机器学习模型对预测STAS具有一定的预测价值,其中基于6 mm瘤周区域的XGB模型表现最优,有望辅助术前评估。展开更多
Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucid...Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways.Methods:Utilizing bioinformatics methodologies,we explored the differential expression of NCAPD2 between normal and tumor samples,along with its correlations with clinical-pathological characteristics,survival prognosis,and immune infiltration.Results:In the TCGA-LUAD dataset,tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples(p<0.001).Clinically,higher NCAPD2 expression was notably associated with advanced T,N,and M stages,pathologic stage,gender,smoking status,and diminished overall survival(OS).Moreover,differentially expressed genes(DEGs)associated with NCAPD2 were predominantly enriched in pathways related to cell division.Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells,naïve CD4+T cells,activated memory CD4+T cells,and M1 macrophages.In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and cell cycle progression.Conclusions:In summary,NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.展开更多
基金supported by Zhongnanshan Medical Foundation of Guangdong Province(No.ZNSXS-20240108 to Anping Xu).
文摘Objectives:The tumorigenic progression of Lung adenocarcinoma(LUAD),the predominant NSCLC subtype,is predominantly driven by co-occurring mutations in KRAS proto-oncogene(KRAS)/Tumor protein p53(TP53).However,their impact on tumor microenvironment(TME)heterogeneity,particularly neutrophil dynamics,remains poorly understood.This present study aims to elucidate how KRAS/TP53 mutations reprogram the TME and develop a neutrophil-centric prognostic signature for LUAD.Methods:Leveraging single-cell RNA sequencing data and transcriptome data,neutrophil subpopulations were identified using Seurat and CellChat R packages,with trajectory analysis via Monocle2 R package.High-dimensional weighted gene co-expression network analysis(hdWGCNA),univariate Cox regression,and least absolute shrinkage and selection operator(LASSO)regression analyses were employed to generate a prognostic signature.Functional validation included Ras homolog family member V(RHOV)knockdown in A549/H1299 cells using siRNA,were assessed by cell counting kit 8(CCK8)assay,wound healing assay,and transwell assay.Results:KRAS/TP53-mutated LUAD exhibited increased neutrophil infiltration,particularly IS MUT subtypes with enhanced OSM/CALCR/IL-1 signaling.A five-gene prognostic signature(MS4A1,ANLN,FAM83A,RHOV,KRT6A)stratified patients into high-and low-risk groups with divergent overall survival in the TCGA-LUAD cohort(p<0.0001).AUCs achieved 0.73,0.70,and 0.66 at 1-,3-,and 5-year,respectively.External validation in immunotherapy cohorts(IMvigor210,GSE78220)confirmed the fine predictive capability of the prognostic signature in predicting treatment response.An integrated prognostic nomogram combining clinicopathological features and risk score further improved its clinical utility.Pseudotime analysis found that RHOV was essential for the growth of lung epithelial cells.RHOV knockdown significantly reduced the proliferation,migration,and invasion capabilities of A549/H1299 cells in vitro.Conclusion:KRAS/TP53 mutations may drive neutrophil heterogeneity in the TME of LUAD,addressing prognostic and therapeutic value.The five-gene signature and RHOV targeting offer translational relevance for risk stratification and therapy.These findings bridge genomic alterations with TME remodeling,advancing precision oncology in LUAD.
基金supported by the 2022 Natural Science Foundation of Fujian Province(No.2022J011486).
文摘Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.
文摘目的:通过双向两样本MR方法探讨皮肌炎(Dermatomyositis, DM)、免疫细胞与肺癌(Lung cancer, LC)之间的因果关系,验证免疫细胞在其中起到的中介作用。方法:使用双向双样本孟德尔随机化(Mendelian Randomization, MR)法分析DM与LC及其各种亚型的因果关系,通过两步法MR探讨免疫细胞在DM与LC及各种亚型之间是否起到中介作用。使用MR-Egger截距法和MR-PRESSO法检查有无水平多效性,Cochran’s Q检查有无异质性。结果:根据MR分析结果,DM会增加患小细胞肺癌(Small cell lung cancer, SCLC)和肺腺癌(Lung adenocarcinoma, LUAD)的风险。38种免疫细胞表型与LC密切相关。其中,效应记忆CD8+ T细胞在CD8+ T细胞中所占的百分比、静息CD4调节性T细胞上CD25的表达水平、IgD− CD38+ B细胞的绝对计数、效应记忆CD8+ T细胞在T细胞中所占的百分比,以及CD33+ HLA-DR+ CD14低表达细胞上CD45的表达水平,都参与介导了DM与LUAD以及小细胞肺癌SCLC之间的因果关系。结论:我们的研究结果表明,DM患者并发LUAD和SCLC发生风险将显著增加。此外,我们发现五种免疫细胞性状(效应记忆CD8+ T细胞在CD8+ T细胞中所占的百分比、静息CD4调节性T细胞上CD25的表达水平、IgD− CD38+ B细胞的绝对计数、效应记忆CD8+ T细胞在T细胞中所占的百分比,以及CD33+ HLA-DR+ CD14低表达细胞上CD45的表达水平)在DM患者并发LC中的发病过程中起到重要作用。针对这些免疫细胞性状的深入研究将进一步明确DM导致LC风险升高的病理生理机制。Objective: To explore the causal relationships among dermatomyositis (DM), immune cells, and lung cancer (LC) through the bidirectional two-sample Mendelian randomization (MR) method, and to verify the mediating role of immune cells in this process. Methods: The bidirectional two-sample Mendelian randomization (MR) method was used to analyze the causal relationships between DM and LC as well as its various subtypes. The two-step MR method was applied to explore whether immune cells played a mediating role between DM and LC and its various subtypes. The MR-Egger intercept method and the MR-PRESSO method were used to check for horizontal pleiotropy, and Cochran’s Q test was used to check for heterogeneity. Results: According to the results of the MR analysis, DM increases the risk of developing small cell lung cancer (SCLC) and lung adenocarcinoma (LUAD). 38 immune cell characteristics were closely related to LC. Among them, the percentage of effector memory CD8+ T cells in CD8+ T cells, the expression level of CD25 on resting CD4 regulatory T cells, the absolute count of IgD− CD38+ B cells, the percentage of effector memory CD8+ T cells in T cells, and the expression level of CD45 on CD33+ HLA-DR+ CD14 low-expression cells all participated in mediating the causal relationships between DM and LUAD as well as SCLC. Conclusion: Our research results indicate that the risk of developing LUAD and SCLC in patients with DM will increase significantly. In addition, we found that five immune cell traits (the percentage of effector memory CD8+ T cells in CD8+ T cells, the expression level of CD25 on resting CD4 regulatory T cells, the absolute count of IgD− CD38+ B cells, the percentage of effector memory CD8+ T cells in T cells, and the expression level of CD45 on CD33+ HLA-DR+ CD14 low-expression cells) play an important role in the pathogenesis of LC in patients with DM. In-depth research on these immune cell traits will further clarify the pathophysiological mechanism by which DM leads to an increased risk of LC.
基金Suzhou Youth Science and Technology Project(Grant Number KJXW2022006)Suzhou Science and Technology Plan Project(Grant Number SKY2022142)。
文摘Background:Circular RNAs play an important role in regulating lung adenocarcinoma(LUAD).Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD.However,the biological mechanism of circ_0015278 in LUAD has not been fully clarified,especially in ferroptosis.Materials and Methods:Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278,subsequently confirmed by luciferase reporter assays.The impact of Circ_0015278 on cell proliferation,migration,invasion,and ferroptosis was investigated through a loss-of-function experiment.A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth.Results:Circ_0015278 exhibited downregulation in LUAD.It inhibited cell proliferation,migration,and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism.Moreover,circ_0015278 suppressed tumour growth in mice.Conclusions:Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD.Furthermore,it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.
文摘Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.
基金supported by the National Natural Science Foundation of China(82173828 and 81874314)the Research Project of the Shanghai Municipal Health Commission(20234Y0082).
文摘Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways.Methods:Utilizing bioinformatics methodologies,we explored the differential expression of NCAPD2 between normal and tumor samples,along with its correlations with clinical-pathological characteristics,survival prognosis,and immune infiltration.Results:In the TCGA-LUAD dataset,tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples(p<0.001).Clinically,higher NCAPD2 expression was notably associated with advanced T,N,and M stages,pathologic stage,gender,smoking status,and diminished overall survival(OS).Moreover,differentially expressed genes(DEGs)associated with NCAPD2 were predominantly enriched in pathways related to cell division.Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells,naïve CD4+T cells,activated memory CD4+T cells,and M1 macrophages.In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and cell cycle progression.Conclusions:In summary,NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.
