G2 and S phase-expressed protein 1 is a biomarker for poor prognosis in lung adenocarcinoma
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PROVIDER: S-EPMC10956967 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:NCAPG2 is a component of the condensin II complex and contributes to chromosome segregation via microtubule-kinetochore attachment during mitosis. It is well known that NCAPG2 plays a critical role in cell mitosis; however, the role of altered NCAPG2 expression and its transcriptional regulatory function in cancer development remains mostly unknown. Here, for the first time we reported that NCAPG2 was evidently increased in non-small cell lung cancer tissues compared to adjacent normal lung tissues. Clinicopathological data analysis showed that NCAPG2 overexpression was significantly correlated with lymph node metastasis and pathologic-Tumour Nodes Metastasen stages, and was an independent prognostic factor in lung adenocarcinoma patients. Moreover, siRNA-mediated knockdown of NCAPG2 could inhibit tumour cell growth of lung adenocarcinoma cells (A549 and H1299) in vitro and could significantly lead to cell cycle arrest in the G2 phase. Furthermore, we found that NCAPG2 silencing significantly decreased the expression levels of G2/M phase cell cycle-related protein expressions (Cyclin B1, Cdc2) and increased the expression levels of p27 and p21 through Western blot analysis. Taken together, we demonstrated that increased NCAPG2 expression could regulate cell proliferation and identified as a poor prognostic biomarker in lung adenocarcinoma.
| S-EPMC5345611 | biostudies-literature
Project description:Despite apparently having completed surgical resection, approximately half of resected early-stage lung cancer patients relapse and die of their disease. Adjuvant chemotherapy reduces this risk by only 5% to 8%. Thus, there is a need for better identifying the drivers of relapse, who benefits from adjuvant therapy, and novel targets in this setting. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and cancer, the role of transketolase (TKT), an enzyme in the nonoxidative branch of the PPP that connects PPP and glycolysis, remains obscure in Lung adenocarcinoma (LUAD). In this study, TKT expression was first identified in The Cancer Genome Atlas (TCGA) and then validated with our database. TKT was upregulated at protein levels in cancer compared with normal tissues (P <0.05), and high TKT expression was associated with advanced tumor stage in our cohorts. Besides, TKT inhibitor promotes tumor cell apoptosis and cell cycle blockade. Clearly, TKT plays a critical role in LUAD progression and prognosis and could be a potential biomarker for prediction of recurrence after lung cancer resection.
| S-EPMC9174852 | biostudies-literature
Project description:FAM72A-D promote the self-renewal of neural progenitor cells. There is accumulating evidence that FAM72 promotes tumorigenicity. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of FAM72A-D in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between FAM72 and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, GEPIA, Metascape, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, FAM72 expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high FAM72 expression levels were correlated with a poor OS in LUAD. Additionally, FAM72 expression was independently associated with OS through a multivariate Cox analysis. GO and GSEA revealed enrichment in mitotic nuclear division and cell cycle. Moreover, high FAM72 expression was associated with poor survival. An analysis of immune infiltration showed that FAM72 is correlated with immune cell infiltration. Finally, we found that the methylation level was associated with prognosis in patients with LUAD. In summary, these results indicate that FAM72 is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.
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Project description:ObjectiveTo explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance.MethodsThe expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis.ResultsAnalysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05).ConclusionFNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.
| S-EPMC9458525 | biostudies-literature
Project description:G2 and S-phase expressed 1 (GTSE1) regulates cell cycle progression in human cancers. However, its significance and mechanism of action in acral melanoma (AM) remain unknown. In the present study, we found that GTSE1 expression was upregulated in advanced stage/metastatic AM tissues and metastatic cell lines, and correlated with higher stage (P = .028) and poor disease-free survival (DFS) in patients with AM (P = .003). Cox regression assays validated GTSE1 expression to be an independent prognostic factor of DFS for patients with AM (P = .004). Ectopic expression of GTSE1 enhanced primary AM cell proliferation, invasion, and migration. Loss-of-function in GTSE1 attenuated metastatic AM cell proliferation and metastatic ability in vitro and in vivo. We additionally observed that inhibition of migration and invasion occurred concomitantly with a GTSE1 knockdown-mediated increase in E-cadherin and decreases in N-cadherin and Slug. We further showed that integrin subunit alpha 2 (ITGA2) interacts with GTSE1 and is a downstream effector of GTSE1. Further, ITGA2 levels were positively correlated with GTSE1 expression in human AM tissues. Ectopic ITGA2 expression rescued siGTSE1-mediated inhibition of migration and invasion, thereby restoring epithelial-to-mesenchymal transition (EMT). In conclusion, GTSE1 expression promotes AM progression and correlates with clinical outcomes of patients with AM, and may represent a promising therapeutic target to suppress AM progression.
| S-EPMC5989838 | biostudies-literature
Project description:Background: Recent studies have demonstrated that creatine can promote tumor metastasis and has implications for immune cell function. SLC6A8 encodes a membrane protein that can transport creatine inside and outside the cell. However, there are currently no studies of SLC6A8 in lung adenocarcinoma (LUAD). Methods: In this study, the expression of SLC6A8 in LUAD was analyzed using the Oncomine database, the Cancer Genome Atlas (TCGA) database, and immunohistochemical staining analysis. Survival analysis of patients with LUAD was performed using the cBioPortal and the Kaplan-Meier Plotter websites and clinical follow-up data. An analysis of the association between SLC6A8 and the tumor immune microenvironment (TIME) of LUAD was performed through the TISIDB database and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm. Then, based on the curated list of SLC6A8-related immunomodulators, three genes (NT5E, CD40LG, CD80) were selected to construct SLC6A8-related immune signatures to further evaluate the immune aspect of LUAD prognosis. Results: Our studies indicated that SLC6A8 was overexpressed in LUAD, and the high expression of SLC6A8 was associated with poor survival. Genetic alteration of SLC6A8 was also associated with a poorer prognosis. Furthermore, multivariate Cox analysis indicated that SLC6A8 could be used as an independent risk prognostic factor. Then, immune infiltration analysis indicated that SLC6A8 was also strongly associated with poor prognosis in the TIME of LUAD. A multivariate Cox proportional hazard model was then constructed, and was shown effective at identifying high-risk patients. Univariate and multivariate Cox analysis showed that the risk scoring of the model was an independent prognostic risk factor in LUAD. Conclusion: SLC6A8 may serve as a biomarker for poor prognosis in LUAD.
| S-EPMC9185669 | biostudies-literature
Project description:BackgroundSpindle and kinetochore associated complex subunit 1/2/3 (SKA1/2/3), which stabilized spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis, were dysregulated, and closely related to prognosis in several malignant tumors. Nevertheless, the potential clinical value of SKA1/2/3, especially in terms of prognosis and development of NSCLC, had not been fully elucidated.MethodsONCOMINE, GEPIA, UALCAN, TCGA, STRING and other databases were used to analyze the expression of SKA1/2/3 in patients with lung adenocarcinoma (LUAD) and its clinical value, and to explore the possible regulatory mechanism of SKA in the occurrence and development of LUAD.ResultsIn patients with LUAD, SKA1/2/3 mRNA expression level was significantly up-regulated, and AUC was 0.9558, 0.7034 and 0.9775, respectively. Increased SKA 1/2/3 expression was associated with smoking, tissue typing, and poor prognosis in LUAD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed that SKA1/2/3 was mainly enriched in DNA replication, cell cycle, homologous recombination, p53 signaling pathway, etc. Hub genes in protein-protein interactions are CDK1, BUB1, CCNA2, CDC20, CCNB2, CCNB1, BUB1B, AURKB, TOP2A and MAD2L1. Hub gene expression in LUAD is increased, and its increased expression is related to poor prognosis of LUAD patients. Finally, the expression of SKA1/2/3 and its correlation with clinicopathological features were verified in 30 clinical LUAD samples.ConclusionsSKA1/2/3 may serve as a potential prognostic biomarker and target for LUAD. In addition, SKA 1/2/3 may affect the prognosis of LUAD through DNA replication, cell cycle, homologous recombination and p53 signaling pathway.
| S-EPMC7225159 | biostudies-literature
Project description:BackgroundBecause of the high incidence and poor prognoses of lung adenocarcinoma (LUAD), it is essential to identify cost-effective treatment options and accurate and reliable prognostic biomarkers. CDCA4 upregulation has been identified in many cancers. However, the prognostic importance of CDCA4 and its role in LUAD remain unknown.MethodsCDCA4 expression was assessed through IHC, Western blotting (WB) and RT-PCR. The Cancer Genome Atlas (TCGA) provided data from 513 patients to study the expression and prognostic relevance of CDCA4 in LUAD. This study used gene set enrichment analyses (GSEA), gene ontology and KEGG pathway analyses for elucidating potential mechanisms underpinning the function of CDCA4 in LUAD. We also investigated correlations between immune infiltration and CDCA4 expression with single specimen GSEA (ssGSEA).ResultsAccording to database analysis and identification of patient tissue samples, CDCA4 expression in tumour tissues surpassed that in normal tissues (P< 0.001). Increased CDCA4 expression was positively correlated with a higher T, N, pathologic stage and poor primary therapy outcome. In addition, the Kaplan-Meier plotter exhibited that an elevated CDCA4 expression was related to worse disease-specific survival(DSS) and overall survival (OS) (DSS HR= 5.145, 95% CI=3.413-7.758, P<0.001; OS HR=3.570, 95% CI=2.472-5.155, P<0.001). Then multivariate COX regression analyses indicated that the CDCA4 gene was an independent risk consideration for prognoses. GO and KEGG results showed that CDCA4 and its neighbouring genes were enriched in the cell cycle and DNA replication. As determined by GSEA, CDCA4 was related to various immune-related signalling pathways (SPs), Homologous recombination, DNA replication and the cell cycle. SsGSEA analysis showed a significant association between CDCA4 expression and Th2 cells, mast cells, eosinophils and Th17 cells.ConclusionsCDCA4 expression is increased in LUAD and is a potential predictive biomarker and therapeutic target.
| S-EPMC9520321 | biostudies-literature
Project description:BackgroundCMTM6 which is chemokine-like factor (CKLF)-like Marvel transmembrane domain containing family member 6 is involved in the occurrence and progression of various tumors. However, the role of CMTM6 is still unclear in lung adenocarcinoma (LUAD).MethodsImmunohistochemical, Western blotting and RT‒PCR methods were used to detect the expression of CMTM6 in LUAD. Cox regression and the Kaplan‒Meier method were performed to assess overall survival. Immunogenic features were evaluated according to immune cell infiltrations, immune checkpoints. The sensitivity to chemotherapy agents was estimated using the pRRophetic package.ResultsIn LUAD, the expression of CMTM6 was obviously upregulated and was significantly associated with T stage (p = 0.008) and lymph node metastasis (p = 0.018). Multivariate Cox regression analysis demonstrated that CMTM6 was a specialty prognostic risk factor. Based on GSEA enrichment analysis, we found that high expression of CMTM6 is associated with multiple immune signaling pathways. The group with high CMTM6 expression showed a positive association with various types of tumor-infiltrating cells. Moreover, a total of 36 chemotherapeutic drugs were significantly correlated with the expression of CMTM6. Among them, two chemotherapeutic drugs had better therapeutic effects in the high CMTM6 expression group, while 34 chemotherapeutic drugs had therapeutic effects in the low CMTM6 expression group.ConclusionThis study confirmed that CMTM6 is highly expressed in LUAD and is a new independent poor prognostic factor. In addition, the high expression of CMTM6 is closely related to the tumor microenvironment and immunotherapy, providing new ideas for the treatment of posterior LUAD.
| S-EPMC9838204 | biostudies-literature
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