Screening and Validation of Significant Genes with Poor Prognosis in Pathologic Stage-I Lung Adenocarcinoma

Deng, Yujie; Chen, Xiaohui; Huang, Chuanbing; Song, Jun; Feng, Sisi; Chen, Xuzheng; Ruixiang, Zhou

doi:10.1155/2022/3794021

Cited by 6 publications

(6 citation statements)

References 50 publications

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“…Etoposide, which targets TOP2A, has been approved for the treatment of small cell lung cancer, but there are currently no drugs for LUAD (48,49). Through various bioinformatics approaches, TOP2A has been identified as an independent factor affecting the prognosis of patients with LUAD (50)(51)(52)(53), whereas an increased TOP2A expression has also been identified as a potential risk factor for pathological stage I LUAD (54). Ciclopirox olamine and quercetin have also been demonstrated to exert tumor-suppressive effects via TOP2A in LUAD (55,56).…”

Section: Discussionmentioning

confidence: 99%

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma

Xu¹,

Wang

Xu³

et al. 2023

Oncol Lett

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The comprehensive analysis of single or multiple microarray datasets is currently available in Gene Expression Omnibus (GEO) databases, with several studies having identified genes strongly associated with the development of lung adenocarcinoma (LUAD). However, the mechanisms of LUAD development remain largely unknown and has not yet been systematically studied; thus, further studies are required in this field. In the present study, weighted gene co-expression network analysis (WGCNA) was used for the evaluation of key genes with potential high risk of LUAD, and to provide more reliable evidence concerning its pathogenesis. The GSE140797 dataset from the high-throughput GEO database was downloaded and was first analyzed using the Limma package in the R language in order to determine the differentially expressed genes. The dataset was then analyzed using the WGCNA package to analyze the co-expressed genes, and the modular genes with the highest correlation with the clinical phenotype were identified. Subsequently, the pathogenic genes shared in common between the result of the two analyses were imported into the STRING database for protein-protein interaction network analysis. The hub genes were screened out using Cytoscape, and then The Cancer Genome Atlas analysis, receiver operating characteristic analysis and survival analysis were subsequently performed. Finally, the key genes were evaluated using reverse transcription-quantitative PCR and western blot analysis. Bioinformatics analysis of the GSE140797 dataset revealed eight key genes: AURKA, BUB1, CCNB1, CDK1, MELK, NUSAP1, TOP2A and PBK. Finally, the AURKA, TOP2A and MELK genes were evaluated in samples from patients with lung cancer using WGCNA and RT-qPCR, western blot analysis experiments, providing basis for further research on the mechanisms of LUAD development and targeted therapy.

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Section: Discussionmentioning

confidence: 99%

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma

Xu¹,

Wang

Xu³

et al. 2023

Oncol Lett

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“…During interphase, the ANLN protein is localized exclusively in the nucleus, whereas it becomes cytoplasmic during mitosis ( 30 ). Furthermore, ANLN has been identified as a poor prognostic marker associated with aggressive cancer phenotypes in multiple types of cancer, including bladder cancer ( 31 ), hepatocellular carcinoma ( 32 ), colorectal cancer ( 33 ), head and neck squamous cell carcinoma ( 34 ) and stage I LUAD ( 14 ). The present study demonstrated that high ANLN expression was significantly associated with clinical stage progression in patients with LUAD and that those exhibiting higher expression levels of ANLN had poorer prognoses.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of ANLN inhibits the progression of lung adenocarcinoma via pyroptosis activation

et al. 2023

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Significant advancements have been achieved in the area of molecular targeted therapy for lung adenocarcinoma (LUAD). However, the complex molecular patterns and high heterogeneity of LUAD confine the efficacy of these therapies to a specific subset of patients; therefore, it is necessary to explore novel targets for LUAD treatment. The expression levels of anillin (ANLN) in LUAD were analyzed using the Gene Expression Profiling Interactive Analysis database. Furthermore, the association between ANLN gene expression and patient survival outcomes was evaluated using the Kaplan-Meier Plotter. Subsequently, small interfering RNA (siRNA) transfection was performed to knock down ANLN in A549 and H1299 cell lines, after which, TUNEL, colony formation and Transwell assays were conducted to assess cell death, colony formation and migration, respectively. Additionally, western blot analysis was performed to analyze the expression levels of caspase-1, interleukin (IL)-18 (IL-18), IL-1β, NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC) and cleaved gasdermin D (GSDMD) following ANLN knockdown. The results revealed that ANLN mRNA expression was significantly increased in LUAD tissues compared with adjacent normal samples. Furthermore, the expression levels of ANLN displayed an increasing trend with advancing clinical stage. Furthermore, patients with high ANLN expression levels exhibited poor overall survival rates compared with those with low ANLN expression levels. Subsequent ANLN knockdown experiments indicated elevated cell death rate, and reduced colony formation and migration in both A549 and H1299 cells. Additionally, ANLN knockdown resulted in increased protein expression levels of pyroptosis-associated molecules, including caspase-1, NLRP3, cleaved-GSDMD, IL-1β, ASC and IL-18 in both A549 and H1299 cells. In conclusion, ANLN represents an important gene and a promising therapeutic target for LUAD. Its potential as a therapeutic target makes it an interesting candidate for further exploration in the development of novel treatment strategies for LUAD.

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“…According to the expression profile of non-small cell lung cancer (NSCLC) obtained from the National Center for Biotechnology Information-Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/), UBE2T is one of the differential genes, and its prognosis risk ratio is the most remarkable. Its increase was identified as a potential risk factor for pathological stage I lung adenocarcinoma (LUAD) (79). Certain differential genes, particularly UBE2T, showed similar survival risks (80).…”

Section: Expression Of Ube2t In Cancermentioning

confidence: 99%

Diverse roles of UBE2T in cancer (Review)

Yan

et al. 2023

Oncol Rep

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As a leading cause of mortalities worldwide, cancer results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in cancer, particularly aberrant ubiquitination, has drawn increasing interest in recent years. The present study aimed to review the roles of ubiquitin-conjugating enzyme E2 T (UBE2T) and its associated pathways in the pathogenesis of pan-cancer, and the development of small-molecule modulators to regulate ubiquitination for treatment strategies. The current study comprehensively investigated the expression landscape and functional significance of UBE2T, as well as its correlation with cancer cell sensitivity to chemotherapy/radiotherapy. Multiple levels of evidence suggested that aberrant UBE2T played important roles in pan-cancer. Information was collected from 16 clinical trials on ubiquitin enzymes, and it was found that these molecules had an important role in the ubiquitin-proteasome system. Further studies are necessary to explore their feasibility and effectiveness as diagnostic and prognostic biomarkers, or as up/down-stream and therapeutic targets for cancer treatment.

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Screening and Validation of Significant Genes with Poor Prognosis in Pathologic Stage-I Lung Adenocarcinoma

Cited by 6 publications

References 50 publications

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma

Knockdown of ANLN inhibits the progression of lung adenocarcinoma via pyroptosis activation

Diverse roles of UBE2T in cancer (Review)

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