Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Li, Feng; Niu, Yandie; Zhao, Wei; Yan, CH

doi:10.1038/s41598-022-23852-z

Cited by 7 publications

(7 citation statements)

References 35 publications

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“…10 PPP1R3G, a member of the PPP1R3 family, is implicated in multiple cellular biological processes, such as cellular proliferation, migration, apoptosis, and necroptosis. 8,11,12 The Human Protein Atlas database confirmed the expression of PPP1R3G in the placenta at the gene and protein level. However, the role of PPP1R3G in PE has not yet been explored.…”

Section: Impact Statementmentioning

confidence: 90%

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway

Shi,

Kong,

Miao

et al. 2023

Exp Biol Med (Maywood)

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Pre-eclampsia (PE) is a severe pregnancy complication characterized by impaired trophoblast invasion and spiral artery remodeling and can have serious consequences for both mother and child. Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is involved in numerous tumor-related biological processes. However, the biological action and underlying mechanisms of PPP1R3G in PE progression remain unclear. We used western blotting and immunohistochemistry to investigate PPP1R3G expression in gestational age-matched pre-eclamptic and normal placental tissues. After lentivirus transfection, wound-healing, Transwell, cell-counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and TdT mediateddUTP Nick End Labeling (TUNEL) assays were used to assess trophoblast migration, invasion, proliferation, and apoptosis, respectively. The relative expression levels of PPP1R3G and the proteins involved in the Akt signaling pathway were determined using western blotting. The results showed that PPP1R3G levels were significantly lower in the placental tissues and GSE74341 microarray of the PE group than those of the healthy control group. We also found that neonatal weight and Apgar score were lower at birth, and peak systolic blood pressure and diastolic blood pressure were higher in the PE group than in the non-PE group. In addition, PPP1R3G knockdown decreased p-Akt/Akt expression and inhibited migration, invasion, and proliferation in HTR-8/SVneo trophoblasts but had no discernible effect on cell apoptosis. Furthermore, PPP1R3G positively regulated matrix metallopeptidase 9 (MMP-9), which was downregulated in placental tissues of pregnant women with PE. These results provided the first evidence that the reduced levels of PPP1R3G might contribute to PE by suppressing the invasion and migration of trophoblasts and targeting the Akt/MMP-9 signaling pathway.

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Section: Impact Statementmentioning

confidence: 90%

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway

Shi,

Kong,

Miao

et al. 2023

Exp Biol Med (Maywood)

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“…VCP (valosin-containing protein) is crucial for maintaining mitochondrial function, and in prostate cancer cells, it employs self-aggregation to inhibit mitochondrial activity, thereby evading cell death during nutrient deprivation and promoting malignancy [ 32 ]. In a cohort study, Tao et al demonstrated that NUPR1 serves as a protective factor in the survival prognosis of LUAD [ 33 ], while Li et al suggested NUPR1 to be a potential risk gene [ 34 ]. NUPR1, a nuclear protein, plays a critical role in redox reactions [ 35 ], and macrophages have been implicated as the most relevant immune cells associated with NUPR1 expression in bladder cancer [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated multi-omic analysis and experiment reveals the role of endoplasmic reticulum stress in lung adenocarcinoma

Liu,

Lin,

Qian

et al. 2024

BMC Med Genomics

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Background Lung cancer is a highly prevalent malignancy worldwide and is associated with high mortality rates. While the involvement of endoplasmic reticulum (ER) stress in the development of lung adenocarcinoma (LUAD) has been established, the underlying mechanism remains unclear. Methods In this study, we utilized data from The Cancer Genome Atlas (TCGA) to identify differentially expressed endoplasmic reticulum stress-related genes (ERSRGs) between LUAD and normal tissues. We performed various bioinformatics analyses to investigate the biological functions of these ERSRGs. Using LASSO analysis and multivariate stepwise regression, we constructed a novel prognostic model based on the ERSRGs. We further validated the performance of the model using two independent datasets from the Gene Expression Omnibus (GEO). Additionally, we conducted functional enrichment analysis, immune checkpoint analysis, and immune infiltration analysis and drug sensitivity analysis of LUAD patients to explore the potential biological function of the model. Furthermore, we conducted a battery of experiments to verify the expression of ERSRGs in a real-world cohort. Results We identified 106 ERSRGs associated with LUAD, which allowed us to classify LUAD patients into two subtypes based on gene expression differences. Using six prognostic genes (NUPR1, RHBDD2, VCP, BAK1, EIF2AK3, MBTPS2), we constructed a prognostic model that exhibited excellent predictive performance in the training dataset and was successfully validated in two independent external datasets. The risk score derived from this model emerged as an independent prognostic factor for LUAD. Confirmation of the linkage between this risk model and immune infiltration was affirmed through the utilization of Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The q-PCR results verified significant differences in the expression of prognostic genes between cancer and paracancer tissues. Notably, the protein expression of NUPR1, as determined by immunohistochemistry (IHC), exhibited an opposite pattern compared to the mRNA expression patterns. Conclusion This study establishes a novel prognostic model for LUAD based on six ER stress-related genes, facilitating the prediction of LUAD prognosis. Additionally, NUPR1 was identified as a potential regulator of stress in LUAD.

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“…Subsequently, we developed a novel prognostic model consisting of seven ERS-related lncRNAs. Previous studies have also constructed ERS-related models in various tumors, such as lung adenocarcinoma, breast cancer, hepatocellular carcinoma, and ovarian cancer [37][38][39][40] . However, the prognostic potential of ERS-related lncRNAs in HNSCC remains largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a prognostic signature based on seven endoplasmic reticulum stress-related lncRNAs for patients with head and neck squamous cell carcinoma

Zhou

et al. 2023

Preprint

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Head and neck squamous cell carcinoma (HNSCC) is the most prevalent form of head and neck cancer, with an escalating incidence rate and dismal survival outcomes. Endoplasmic reticulum stress (ERS) occurs when misfolded or unfolded proteins accumulate in the endoplasmic reticulum (ER), and it is often observed in tumors, including HNSCC. Relevant studies have demonstrated the prognostic significance of ERS-related long non-coding RNAs (lncRNAs) in various cancers. However, the relationship between ERS and lncRNAs in HNSCC has received limited attention in previous studies. Based on this, we aimed to identify the lncRNAs that impact the clinical prognosis of HNSCC patients and develop an ERS-related lncRNA prognostic model in this study. Transcriptomic, gene mutation, and clinical data were acquired from The Cancer Genome Atlas (TCGA) database. Correlation analysis, Cox regression analysis, and least absolute shrinkage, and selection operator (LASSO) regression analysis were used to establish an ERS-related lncRNAs prognostic model. Subsequently, the survival and predictive ability of this model were evaluated using Kaplan-Meier analysis and time-dependent receiver operating characteristics (ROC), while nomograms and calibration curves were constructed. Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) functional enrichment analyses, tumor mutation burden (TMB), tumor infiltration of immune cells, single sample Gene Set Enrichment Analysis (ssGSEA), drug sensitivity analysis were performed. Furthermore, we conducted a consensus cluster analysis to compare differences between subtypes of tumors. Finally, we validated the expression of the seven lncRNAs in HNSCC tissues through qRT-PCR. A total of 423 lncRNAs were identified as ERS-related lncRNAs in HNSCC tissues. The prognostic signature was established based on seven ERS-related lncRNAs, namely ACTN1-AS1, AP003774.2, DOCK8-AS1, DDX11-AS1, MIR924HG, MIR9-3HG, and AL451085.2. The high-risk group had a poorer prognosis in comparison to the low-risk group. As an independent predictor, the model showed better predictive performance than other clinicopathological features. The area under the ROC curve (AUC) predicted by this model for 3-year survival rates of HNSCC patients was 0.805. Enrichment analysis revealed that the differentially expressed genes were primarily enriched in pathways related to immune responses and signal transduction. Low-risk patients had lower TMB, more immune cell infiltrations, and enhanced anti-tumor immunity. Cluster analysis indicated that cluster 3 may have a better prognosis and immunotherapy effect. In addition, the result of qRT-PCR was consistent with our analysis. This prognostic model based on seven ERS-related lncRNAs is a promising tool for risk stratification, survival prediction, and immune cell infiltration status assessment.

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Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Cited by 7 publications

References 35 publications

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway

Integrated multi-omic analysis and experiment reveals the role of endoplasmic reticulum stress in lung adenocarcinoma

Construction and validation of a prognostic signature based on seven endoplasmic reticulum stress-related lncRNAs for patients with head and neck squamous cell carcinoma

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