Alternatively Expressed Transcripts Analysis of Non-Small Cell Lung Cancer Cells under Different Hypoxic Microenvironment

Wang, Shunjun; Ma, HuSai; Li, Huayang; Liu, Quan; Huang, Sheng; Huang, Lin; Luo, Li; Jiang, Yupeng; Wu, Zhongkai

doi:10.1155/2021/5558304

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…Our findings indicated that the risk score formula was associated with PFS and treatment responses in patients with NSCLC undergoing anti-PD-1/PD-L1 therapy. The IMvigor210 study examined the effect of PD-L1 inhibitor treatment in patients with metastatic urothelial cancer ( Mariathasan et al, 2018 ; Wang S. et al, 2021 ). Because relatively few patients were enrolled in the GSE135222 and GSE126044 cohorts, we further evaluated the formula in the IMvigor210 cohort.…”

Section: Discussionmentioning

confidence: 99%

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Ouyang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model for evaluating the risk of LUAD based on hypoxia, immunity, and epithelial-mesenchymal transition (EMT) gene signatures.Methods: In this study, we used data from TCGA-LUAD for the training cohort and GSE68465 and GSE72094 for the validation cohorts. Immunotherapy datasets GSE135222, GSE126044, and IMvigor210 were obtained from a previous study. Using bioinformatic and machine algorithms, we established a risk model based on hypoxia, immune, and EMT gene signatures, which was then used to divide patients into the high and low risk groups. We analyzed differences in enriched pathways between the two groups, following which we investigated whether the risk score was correlated with stemness scores, genes related to m6A, m5C, m1A and m7G modification, the immune microenvironment, immunotherapy response, and multiple anti-cancer drug sensitivity.Results: Overall survival differed significantly between the high-risk and low-risk groups (HR = 4.26). The AUCs for predicting 1-, 3-, and 5-year survival were 0.763, 0.766, and 0.728, respectively. In the GSE68465 dataset, the HR was 2.03, while the AUCs for predicting 1-, 3-, and 5-year survival were 0.69, 0.651, and 0.618, respectively. The corresponding values in the GSE72094 dataset were an HR of 2.36 and AUCs of 0.653, 0.662, and 0.749, respectively. The risk score model could independently predict OS in patients with LUAD, and highly correlated with stemness scores and numerous m6A, m5C, m1A and m7G modification-related genes. Furthermore, the risk model was significantly correlated with multiple immune microenvironment characteristics. In the GSE135222 dataset, the HR was 4.26 and the AUC was 0.702. Evaluation of the GSE126044 and IMvigor210 cohorts indicated that PD-1/PD-LI inhibitor treatment may be indicated in patients with low risk scores, while anti-cancer therapy with various drugs may be indicated in patients with high risk scores.Conclusion: Our novel risk model developed based on hypoxia, immune, and EMT gene signatures can aid in predicting clinical prognosis and guiding treatment in patients with LUAD.

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Section: Discussionmentioning

confidence: 99%

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Ouyang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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“…Another study proved that DDX49 participated in the promotion of the growth of NSCLC cells and lymph node metastasis via increasing the Akt/β-catenin pathway ( Lian et al, 2020 ). In NSCLC, KXD1 overexpression was positively correlated with cancer invasion and metastasis and negatively correlated with non-surgical anti-cancer treatment resistance ( Wang et al, 2021 ). NR2C2AP, which was highly expressed in NSCLC, also known as TRA16, could promote cancer cell growth by enhancing the ERβ signaling pathway and was associated with lymph node metastasis and poor OS ( Fang et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases

et al. 2022

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Background: Hepatocellular carcinoma (HCC) is a solid tumor with high recurrence rate and high mortality. It is crucial to discover available biomarkers to achieve early diagnosis and improve the prognosis. The effect of LSM4 in HCC still remains unrevealed. Our study is dedicated to exploring the expression of LSM4 in HCC, demonstrating its clinical significance and potential molecular mechanisms.Methods: Clinical information and LSM4 expression values of HCC were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prognostic and diagnostic significance of LSM4. Calculating pooled standardized mean difference (SMD) and performing summary receiver operating characteristic (sROC) curve analysis to further determine its expression status and diagnostic significance. LSM4-related co-expressed genes (CEGs) were obtained and explored their clinical significance in HCC. LSM4-associated pathways were identified through Gene set enrichment analysis (GSEA).Results: Up-regulated LSM4 was detected in HCC tissues (SMD = 1.56, 95% CI: 1.29–1.84) and overexpressed LSM4 had excellent distinguishing ability (AUC = 0.91, 95% CI: 0.88–0.93). LSM4 was associated with clinical stage, tumor grade, and lymph node metastasis status (p < 0.05). Survival analysis showed that high LSM4 expression was related to poor overall survival (OS) of HCC patients. Cox regression analysis suggested that high LSM4 expression may be an independent risk factor for HCC. We obtained nine up-regulated CEGs of LSM4 in HCC tissues, and six CEGs had good prognostic and diagnostic significance. GSEA analysis showed that up-regulated LSM4 was closely related to the cell cycle, cell replication, focal adhesion, and several metabolism-associated pathways, including fatty acid metabolism.Conclusion: Overexpressed LSM4 may serve as a promising diagnostic and prognostic biomarker of HCC. Besides, LSM4 may play a synergistic effect with CEGs in promoting the growth and metastasis of HCC cells via regulating crucial pathways such as cell cycle, focal adhesion, and metabolism-associated pathways.

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“…LUAD is a major type of lung cancer with a high incidence rate ( Li Z. et al, 2021 ; Wang et al, 2021 ). The prognosis of LUAD remains devastating because of its obscure pathogenesis ( Peng et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma

Jiang

Ouyang

Zhang

et al. 2022

Front. Cell Dev. Biol.

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The Golgi apparatus (GA) is a cellular organelle that participates in the packaging, modification, and transport of proteins and lipids from the endoplasmic reticulum to be further fabricated before being presented to other cellular components. Recent studies have demonstrated that GA facilitates numerous cellular processes in cancer development. Therefore, this study aimed to establish a novel lung adenocarcinoma (LUAD) risk evaluation model based on GA gene signatures. In this study, we used TCGA-LUAD (n = 500) as the training cohort and GSE50081 (n = 127), GSE68465 (442), and GSE72094 (398) as the validation cohorts. Two immunotherapy datasets (GSE135222 and GSE126044) were also obtained from a previous study. Based on machine algorithms and bioinformatics methods, a GA gene-related risk score (GARS) was established. We found that the GARS independently predicted the prognosis of LUAD patients and remained effective across stages IA to IIIA. Then, we identified that the GARS was highly correlated with mutations in P53 and TTN. Further, this study identified that GARS is related to multiple immune microenvironmental characteristics. Furthermore, we investigated GSE135222 and GSE126044 and found that a lower GARS may be indicative of an improved therapeutic effect of PD-1/PD-L1 therapy. We also found that high GARS may lead to a better response to multiple anticancer drugs. Finally, we established a nomogram to better guide clinical application. To our knowledge, this is the first study to demonstrate a novel GA signature-based risk score formula to predict clinical prognosis and guide the treatment of LUAD patients.

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Alternatively Expressed Transcripts Analysis of Non-Small Cell Lung Cancer Cells under Different Hypoxic Microenvironment

Cited by 5 publications

References 30 publications

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases

Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma

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