Development of a novel prognostic score combining clinicopathologic variables, gene expression, and mutation profiles for lung adenocarcinoma

Li, Guofeng; Wang, Guangsuo; Guo, Yanhua; Li, Shixuan; Zhang, Youlong; Li, Jialu; Peng, Bin

doi:10.1186/s12957-020-02025-0

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Some scholars have also found some genes related to the differences and prognosis through biological information analysis [ 15 , 22 – 24 ], for example, EGFR, KRAS, PIK3CA, STEAP1/2, HOXA11, and TCN1. In addition, some scholars analyze its application value in clinical diagnosis and treatment by constructing a new prognostic model [ 14 , 21 , 25 , 26 ]. Therefore, the combination of bioinformatics technology to find possible diagnostic and prognostic markers of lung adenocarcinoma has become the key point.…”

Section: Discussionmentioning

confidence: 99%

UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma

et al. 2022

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Background Lung adenocarcinoma is the leading cause of cancer death worldwide. Recently, ubiquitin C-terminal hydrolase L1 (UCHL1) has been demonstrated to be highly expressed in many tumors and plays the role of an oncogene. However, the functional mechanism of UCHL1 is unclear in lung adenocarcinoma progression. Methods We analyzed the differential expression of the UCHL1 gene in lung adenocarcinoma and normal lung tissues, and the correlation between the UCHL1 gene and prognosis was also analyzed by the bioinformatics database TCGA. Meanwhile, we detected and analyzed the expression of UCHL1 and Ki-67 protein in a tissue microarray (TMA) containing 150 patients with lung adenocarcinoma by immunohistochemistry (IHC) and clinicopathological characteristics by TCGA database. In vitro experiments, we knocked down the UCHL1 gene of A549 cells and detected the changes in cell migration, invasion, and apoptosis. At the same time, we analyzed the effect of UCHL1 on anti-tumor drug sensitivity of lung adenocarcinoma by a bioinformatics database. In terms of the detection rate of lung adenocarcinoma indicators, we analyzed the impact of UCHL1 combined with common clinical indicators on the detection rate of lung adenocarcinoma through a bioinformatics database. Results In this study, the analysis of UCHL1 protein expression in lung adenocarcinoma proved that obviously higher UCHL1 protein level was discovered in lung adenocarcinoma tissues. The expression of UCHL1 was closely related to poor clinical outcomes. Interestingly, a significantly positive correlation between the expression of UCHL1 and Ki-67-indicated UCHL1 was associated with tumor migration and invasion. Through executing loss of function tests, we affirmed that silencing of UCHL1 expression significantly inhibited migration and invasion of lung adenocarcinoma cells in vitro. Furthermore, lung adenocarcinoma cells with silenced UCHL1 showed a higher probability of apoptosis. In terms of the detection rate of lung adenocarcinoma indicators, we discovered UCHL1 could improve the detection rate of clinical lung adenocarcinoma and affect drug sensitivity. Conclusion In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma. In addition, UCHL1 can improve the detection rate of clinical lung adenocarcinoma. Above all, UCHL1 may be a new marker for the diagnosis of lung adenocarcinoma and provide a new target for the treatment of clinical diseases.

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Section: Discussionmentioning

confidence: 99%

UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma

et al. 2022

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“…Xu et al [ 13 ] applied protein interaction network mining to identify seven key genes in LUAD and validated that the high expression of these genes is related to adverse prognosis and may improve the response to immunotherapy. Peng et al [ 14 ] integrated gene expression and mutation characteristics and developed a 14-gene prognostic model to evaluate tumor progression in LUAD. Although there have been a large number of biomarkers, they are rarely used in clinic practice, which suggests that effective biomarkers need to be further verified to better guide the treatment of LUAD.…”

Section: Introductionmentioning

confidence: 99%

Identification of a TGF-β signaling-related gene signature for prediction of immunotherapy and targeted therapy for lung adenocarcinoma

Zhao

Yan

et al. 2022

World J Surg Onc

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Background Transforming growth factor (TGF)-β signaling functions importantly in regulating tumor microenvironment (TME). This study developed a prognostic gene signature based on TGF-β signaling-related genes for predicting clinical outcome of patients with lung adenocarcinoma (LUAD). Methods TGF-β signaling-related genes came from The Molecular Signature Database (MSigDB). LUAD prognosis-related genes were screened from all the genes involved in TGF-β signaling using least absolute shrinkage and selection operator (LASSO) Cox regression analysis and then used to establish a risk score model for LUAD. ESTIMATE and CIBERSORT analyzed infiltration of immune cells in TME. Immunotherapy response was analyzed by the TIDE algorithm. Results A LUAD prognostic 5-gene signature was developed based on 54 TGF-β signaling-related genes. Prognosis of high-risk patients was significantly worse than low-risk patients. Both internal validation and external dataset validation confirmed a high precision of the risk model in predicting the clinical outcomes of LUAD patients. Multivariate Cox analysis demonstrated the model independence in OS prediction of LUAD. The risk model was significantly related to the infiltration of 9 kinds of immune cells, matrix, and immune components in TME. Low-risk patients tended to respond more actively to anti-PD-1 treatment, while high-risk patients were more sensitive to chemotherapy and targeted therapy. Conclusions The 5-gene signature based on TGF-β signaling-related genes showed potential for LUAD management.

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“…Although considerable advancement has been made on the diagnosis and treatment of NSCLC, the clinical outcome of NSCLC patients is still unsatisfactory [ 2 ]. The development of novel diagnostic and prognostic targets is under active investigation for NSCLC [ 3 ]. Therefore, disclosing the pathogenesis of NSCLC is essential to identify novel diagnostic and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circVAPA contributes to non-small-cell lung cancer progression via miR-342-3p-dependent regulation of ZEB2

et al. 2021

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Background Accumulating evidence demonstrated that circular RNAs (circRNAs) play pivotal regulatory roles in the pathology of cancers. Disclosing the roles and molecular mechanisms of circRNAs in tumorigenesis and development is essential to identify novel diagnostic and therapeutic targets. In this study, we explored the role of circVAPA in non-small-cell lung cancer (NSCLC) progression and its associated mechanism. Methods The expression level of RNA was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by MTT assay and colony-forming assay. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were assessed by transwell assays. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to test the intermolecular interactions. The role of circVAPA was assessed in vivo. And xenograft tumor tissues were analyzed by immunohistochemistry (IHC) staining. Results CircVAPA expression was upregulated in NSCLC tissues and cell lines, and a high level of circVAPA was associated with a poor prognosis of NSCLC patients. CircVAPA silencing suppressed the proliferation, migration, and invasion and induced the apoptosis of NSCLC cells. CircVAPA served as a molecular sponge for microRNA-342-3p (miR-342-3p). miR-342-3p interference largely reversed circVAPA knockdown-mediated anti-tumor effects in NSCLC cells. Zinc finger E-box-binding homeobox 2 (ZEB2) was a target of miR-342-3p, and miR-342-3p overexpression suppressed the malignant behaviors of NSCLC cells largely by downregulating ZEB2. CircVAPA silence repressed xenograft tumor growth in vivo, and IHC assay confirmed that circVAPA silence restrained the proliferation and metastasis but induced the apoptosis of NSCLC cells in vivo. Conclusion CircVAPA contributes to the progression of NSCLC by binding to miR-342-3p to upregulate ZEB2. CircVAPA/miR-342-3p/ZEB2 axis might be a novel potential target for NSCLC treatment.

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Development of a novel prognostic score combining clinicopathologic variables, gene expression, and mutation profiles for lung adenocarcinoma

Cited by 5 publications

References 43 publications

UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma

UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma

Identification of a TGF-β signaling-related gene signature for prediction of immunotherapy and targeted therapy for lung adenocarcinoma

Circular RNA circVAPA contributes to non-small-cell lung cancer progression via miR-342-3p-dependent regulation of ZEB2

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