NUF2 Expression Promotes Lung Adenocarcinoma Progression and Is Associated With Poor Prognosis.
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ABSTRACT:
SUBMITTER: Jiang F
PROVIDER: S-EPMC9259841 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Topoisomerase IIA (TOP2A) gene encodes DNA topoisomerase enzyme and has been reported that TOP2A is broadly expressed in many types of cancers. Our study aims to investigate the prognostic effect of TOP2A on lung adenocarcinoma (LUAD) and the potential molecular mechanism of TOP2A to tumorigenesis. Methods: Bioinformatical analysis, real-time PCR and Western blot were applied to explore the expression level of TOP2A. Kaplan-Meier survival analysis was used to evaluate the effect of TOP2A on patients' prognosis. Cell proliferation, migration and invasion ability were examined by colony-formation, Cell Counting Kit-8 (CCK8) assay, wound healing assay and transwell invasion assay, respectively. Results: We firstly investigated differentially expressed genes in lung adenocarcinoma and normal tissues of GEO (tumor = 666, normal = 184) and TCGA (tumor = 517, normal = 59) and these data showed that TOP2A is broadly expressed in LUAD and the expression level of TOP2A is associated with poor prognosis, which indicated that TOP2A is an upregulated prognostic related gene in LUAD. Then we identified that the expression level of TOP2A was upregulated in both surgically removed lung cancer tissues and lung cancer cell lines. Knockdown of TOP2A in A549 and GLC82 cells inhibited cell proliferation, migration and invasion. Inhibition of TOP2A reduced the expression levels of CCNB1 and CCNB2, which indicated that TOP2A targeting CCNB1 and CCNB2 promotes GLC82 and A549 cells proliferation and metastasis. Conclusions: Our study revealed an important role of TOP2A in LUAD, and may provide a potential prognostic indicator and target for cancer therapy.
| S-EPMC7066024 | biostudies-literature
Project description:Aberrant epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer (NSCLC) is linked to tumor progression, metastasis and poor survival rates. Here we report the role of Cdc42-interacting protein 4 (CIP4) in the regulation of NSCLC cell invasiveness and tumor metastasis. CIP4 was highly expressed in a panel of NSCLC cell lines and normal lung epithelial cell lines. Stable knockdown (KD) of CIP4 in lung adenocarcinoma H1299 cells, expressing wild-type EGFR, led to increased EGFR levels on the cell surface and defects in sustained activation of Erk kinase in H1299 cells treated with EGF. CIP4 localized to leading edge projections in NSCLC cells, and CIP4 KD cells displayed defects in EGF-induced cell motility and invasion through extracellular matrix. This correlated with reduced expression and activity of matrix metalloproteinase-2 (MMP-2) in CIP4 KD cells compared with control. In xenograft assays, CIP4 silencing had no effect on tumor growth but resulted in significant defects in spontaneous metastases to the lungs from these subcutaneous tumors. This correlated with reduced expression of the Erk target gene Zeb1 and the Zeb1 target gene MMP-2 in CIP4 KD tumors compared with control. CIP4 also enhanced rates of metastasis to the liver and lungs in an intrasplenic experimental metastasis model. In human NSCLC tumor sections, CIP4 expression was elevated greater than or equal to twofold in 43% of adenocarcinomas and 32% of squamous carcinomas compared with adjacent normal lung tissues. Analysis of microarray data for NSCLC patients also revealed that high CIP4 transcript levels correlated with reduced overall survival. Together, these results identify CIP4 as a positive regulator of NSCLC metastasis and a potential poor prognostic biomarker in lung adenocarcinoma.
| S-EPMC4978543 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.
| S-EPMC10907829 | biostudies-literature
Project description:BackgroundOvarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves "recoding" of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated.Materials and methodsWe analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer.ResultsThe expression of DGAT1 was elevated in advanced (p = 0.0432), poorly differentiated (p = 0.0148), and vascular invaded (p = 0.0002) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process.ConclusionDGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.
| S-EPMC8141271 | biostudies-literature
Project description:BackgroundOur previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD.MethodsThe relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798.ResultsThe analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib.ConclusionsCA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD.
| S-EPMC10035219 | biostudies-literature
Project description:Janus kinase 1 (JAK1) is a member of the JAK family, which plays an essential and non-redundant role in tumorigenesis. However, the potential role of JAK1 in immune infiltration and prognosis of lung adenocarcinoma (LUAD) remains unclear. The mRNA expression and methylation level of JAK1 in LUAD were examined using the Oncomine and The Cancer Genome Atlas (TCGA) databases, respectively. The correlations between JAK1 expression and its methylation level and clinicopathological parameters were analyzed. The Kaplan-Meier plotter database was used to evaluate the prognostic value of JAK1 in LUAD. The signaling pathways associated with JAK1 expression were identified by performing a GSEA. The CIBERSORT and TIMER databases were used to analyze the correlations between JAK1 and tumor-infiltrating immune cells. In addition, the JAK1 expression and proportion of immune cells in LUAD cell lines were analyzed. The JAK1 expression was remarkably decreased in patients with LUAD and significantly correlated with the clinical features of patients with LUAD. The JAK1 methylation level was increased and negatively correlated with its mRNA expression. A decrease in JAK1 expression was correlated with poor prognosis. The results of GSEA showed that cell adhesion, tumorigenesis, and immune-related signaling pathways were mainly enriched. JAK1 was positively associated with tumor-infiltrating immune cells, and the results of CIBERSORT analysis suggested that JAK1 was correlated with monotypes and M1 macrophages. The results of the TIMER database analysis confirmed that JAK1 was closely associated with the gene markers of M1 macrophages. Thus, JAK1 may serve as a potential prognostic biomarker in LUAD and is associated with immune infiltration.
| S-EPMC7880401 | biostudies-literature
Project description:BackgroundInterleukin 6 (IL6) is both a pleiotropic cytokine and an immune-related gene. Interleukin 6 receptor (IL6R) is the receptor for IL6. It may be closely connected to the development of lung cancer. This research aims to explore the prognostic value of IL6R and prevent overtreatment of patients with lung adenocarcinoma (LUAD).MethodsIn this study, the expression of IL6R in tumor tissues and surrounding tissues was first analyzed by immunohistochemistry in the Affiliated Hospital of Nantong University (NTU) cohort. Secondly, we downloaded information from The Cancer Genome Atlas (TCGA) for the TCGA cohort and used this information to explore the messenger RNA (mRNA) level of IL6R. We then used Kaplan-Meier survival analyses, univariate and multivariate Cox analyses, nomogram models, and decision curve analyses to assess the prognostic value of IL6R. In addition, we also analyzed immune cell infiltration and the signaling pathways related to IL6R through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).ResultsThrough the data analysis of the NTU cohort and the TCGA cohort, it was found that the expression of IL6R in normal tissues around the tumor was higher than that in tumor tissue, and was positively correlated with the overall survival (OS) of LUAD patients. Additionally, low expression of IL6R was found to be an independent predictor of poor prognosis among the patients in these two research cohorts. Next, using GO, KEGG, and GSEA analyses, we found that partially infiltrated tumor immune cells might be related to earlier staging and better prognosis of patients with LUAD. Finally, the study of the 3-5-year survival rate of LUAD patients through the nomogram showed that the expression of IL6R could improve the accuracy of prediction to prevent the overtreatment of some LUAD patients.ConclusionsIn summary, our study indicated that the low expression of IL6R was associated with poor prognosis among LUAD patients and that low expression of IL6R is a potential independent risk factor that could provide a basis for strengthening postoperative classification management of such patients.
| S-EPMC8339841 | biostudies-literature
Project description:IntroductionLung adenocarcinoma (LUAD) is the most common type of lung cancer. DEP domain-containing 1 B (DEPDC1B) is involved in the development of several cancers; however, its role in LUAD is unknown. Therefore, we aimed to determine the biological function and prognostic value of DEPDC1B in LUAD.Material and methodsWe analyzed the correlation between DEPDC1B expression and the clinical features of LUAD and lung squamous cell carcinoma (LUSC). Survival was evaluated by generating Kaplan-Meier curves, which were used to analyze the relationship between DEPDC1B expression and prognosis in LUAD and LUSC. DEPDC1B expression in tumor and normal tissues from patients with LUAD and LUSC was determined using immunohistochemistry, and its clinical significance was analyzed. Finally, the correlation between the expression and biological function of DEPDC1B in LUAD was examined.ResultsOur findings revealed that DEPDC1B expression was higher in tumor tissues than that in normal tissues from patients with LUAD and LUSC (P < 0.001). These results were confirmed in clinical samples from patients using immunohistochemistry. Analysis of a dataset from The Cancer Genome Atlas (TCGA) showed that high DEPDC1B expression was associated with poor prognosis only in patients with LUAD (P < 0.001). Similarly, high DEPDC1B expression was related to shorter overall survival (OS) and progression-free interval (PFI) in patients with LUAD. These associations were not observed in LUSC. Functional enrichment analysis suggested that DEPDC1B promoted tumor development in LUAD by regulating the cell cycle.ConclusionHigh DEPDC1B expression predicts poor prognosis in patients with LUAD. Thus, DEPDC1B has potential as a therapeutic target for LUAD.
| S-EPMC9332445 | biostudies-literature
Project description:Recently, studies have shown that the up-regulation of Non-SMC Condensin I Complex Subunit G (NCAPG) in some tumors can promote tumor progression, and its high expression has a strong correlation with the poor prognosis of patients. However, there are few studies on NCAPG in lung adenocarcinoma (LUAD). Our research is to explore the role of NCAPG in LUAD and try to reveal the possible molecular mechanism. We use public databases and tissue samples from LUAD patients to verify that NCAPG is significantly up-regulated in LUAD, and the high expression of NCAPG is related to the poor prognosis of patients. Subsequently, we found that silencing NCAPG can inhibit the proliferation and invasion of LUAD cells in vitro and the growth of subcutaneous tumors in nude mice in vivo. In order to explore the possible molecular mechanism of NCAPG's function, we found out the genes co-expressed with NCAPG through the cBioportal database, and discovered that these genes were significantly enriched in the cell cycle and other pathways through DAVID analysis, which implies the importance of NCAPG in the cell cycle. Finally, we confirmed by flow cytometry that NCAPG affects the conversion of cell cycle mitosis from G1 to S. Taken together, our research results suggest that NCAPG plays a role in the progress of LUAD. Moreover, NCAPG can be used as a potential biomarker for the diagnosis of LUAD, as well as a potential therapeutic target for patients with LUAD.
| S-EPMC8974211 | biostudies-literature
Project description:Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p=0.015). ActA levels also correlated with more advanced disease stage (p<0.0001) and T (p=0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients (p<0.001). High serum ActA level was associated with poor overall survival (p<0.0001) and was confirmed as an independent prognostic factor (p=0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases.
| S-EPMC4924649 | biostudies-literature