Lamprey Immune Protein Mediates Apoptosis of Lung Cancer Cells Via the Endoplasmic Reticulum Stress Signaling Pathway

Song, Xiaoping; Xu, Xiaoli; Lü, Jian; Chi, Xiaoyuan; Pang, Yue; Li, Qingwei

doi:10.3389/fonc.2021.663600

Cited by 9 publications

(2 citation statements)

References 32 publications

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“…Apoptosis in lungs is strongly linked with both small cell lung cancer (NSCLC) and non-small cell lung cancer (NSCLC) [210,211]. The extrinsic and intrinsic pathways of apoptosis can be distinguished in lung carcinoma.…”

Section: Lung Cancermentioning

confidence: 99%

Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context

Saddam,

Paul,

Habib

et al. 2024

Egypt J Med Hum Genet

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Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues, and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis-inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning, and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, multiple sclerosis, diabetes. In this review, we addressed the genetic information and structural homology of BCL-2 family members. Further, we elucidate the pro-apoptotic and anti-apoptotic roles of the family members. This review highlights the most recent developments in the BCL-2 protein family and presents evidence that targeting this family proteins may have a positive impact on the treatment of medical problems that are still underserved.

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Section: Lung Cancermentioning

confidence: 99%

Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context

Saddam,

Paul,

Habib

et al. 2024

Egypt J Med Hum Genet

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“…A study reported that ER stress was upregulated by the overexpression of POU4F3 and therefore inhibits tumor progression in LUAD ( 10 ). ROS-mediated ER stress suppresses tumors in lung cancer cells ( 11 ). ER stress pathway can be upregulated by neutrophil arginase-1, released from activated human neutrophils or dead cells, and induces apoptosis of cancer cells ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a prognosis prediction model based on 18 endoplasmic reticulum stress-related genes for patients with lung adenocarcinoma

2022

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BackgroundEndoplasmic reticulum (ER) stress had a crucial impact on cell survival, proliferation, and metastasis in various cancers. However, the role of ER stress in lung adenocarcinoma remains unclear.MethodGene expression and clinical data of lung adenocarcinoma (LUAD) samples were extracted from The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. ER stress score (ERSS) was constructed based on hub genes selected from 799 ER stress-related genes by least absolute shrinkage and selection operator (LASSO) regression. A Cox regression model, integrating ERSS and the TNM stage, was developed to predict overall survival (OS) in TCGA cohort and was validated in GEO cohorts. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and gene mutation analyses were performed to further understand the molecular features of ERSS. The tumor immune infiltration was evaluated by ESTIMATE, CIBERSORT, and xCell algorithms. The receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the risk model. p< 0.05 was considered statistically significant.ResultsOne hundred fifty-seven differentially expressed genes (DEGs) were identified between tumor and para-carcinoma tissues, and 45 of them significantly correlated with OS. Next, we identified 18 hub genes and constructed ERSS by LASSO regression. Multivariate analysis demonstrated that higher ERSS (p< 0.0001, hazard ratio (HR) = 3.8, 95%CI: 2.8–5.2) and TNM stage (p< 0.0001, HR = 1.55, 95%CI: 1.34–1.8) were independent predictors for worse OS. The prediction model integrating ERSS and TNM stage performed well in TCGA cohort (area under the curve (AUC) at five years = 0.748) and three GEO cohorts (AUC at 5 years = 0.658, 0.717, and 0.739). Pathway enrichment analysis showed that ERSS significantly correlated with unfolded protein response. Meanwhile, pathways associated with the cell cycle, growth, and metabolism were significantly enriched in the high ERSS group. Patients with SMARCA4, TP53, and EGFR mutations showed significantly higher ERSS (p = 4e−04, 0.0027, and 0.035, respectively). Tissues with high ERSS exhibited significantly higher infiltration of M1 macrophages, activated dendritic cells, and lower infiltration of CD8+ T cells and B cells, which indicate an activated tumor antigen-presenting but suppressive immune response status.ConclusionWe developed and validated an ER stress-related risk model that exhibited great predictive value for OS in patients with LUAD. Our work also expanded the understanding of the role of ER stress in LUAD.

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The endoplasmic reticulum stress-related genes and molecular typing predicts prognosis and reveals characterization of tumor immune microenvironment in lung squamous cell carcinoma

Wang,

Huang,

et al. 2024

Discov Onc

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Background Endoplasmic reticulum stress (ERS) acts critical roles on cell growth, proliferation, and metastasis in various cancers. However, the relationship between ERs and lung squamous cell carcinoma (LUSC) prognoses still remains unclear. Methods The consensus clustering analysis of ERS-related genes and the differential expression analysis between clusters were investigated in LUSC based on TCGA database. Furthermore, ERS-related prognostic risk models were constructed by LASSO regression and Cox regression analyses. Then, the predictive effect of the risk model was evaluated by Kaplan–Meier, Cox regression, and ROC Curve analyses, as well as validated in the GEO cohort. According to the optimal threshold, patients with LUSC were divided into high- and low- risk groups, and somatic mutations, immune cell infiltration, chemotherapy response and immunotherapy effect were systematically analyzed. Results Two ERS-related clusters were identified in patients with LUSC that had distinct patterns of immune cell infiltration. A 5-genes ERS-related prognostic risk model and nomogram were constructed and validated. Kaplan–Meier curves and Cox regression analysis showed that ERS risk score was an independent prognostic factor (p < 0.001, HR = 1.317, 95% CI = 1.159–1.496). Patients with low-risk scores presented significantly lower TIDE scores and significantly lower IC50 values for common chemotherapy drugs such as cisplatin and gemcitabine. Conclusion ERS-related risk signature has certain prognostic value and may be a potential therapeutic target and prognostic biomarker for LUSC patients.

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Lamprey Immune Protein Mediates Apoptosis of Lung Cancer Cells Via the Endoplasmic Reticulum Stress Signaling Pathway

Cited by 9 publications

References 32 publications

Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context

Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context

Development and validation of a prognosis prediction model based on 18 endoplasmic reticulum stress-related genes for patients with lung adenocarcinoma

The endoplasmic reticulum stress-related genes and molecular typing predicts prognosis and reveals characterization of tumor immune microenvironment in lung squamous cell carcinoma

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