A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer

Mo, Jiahang; Ruan, Shengping; Yang, Baofeng; Jin, Yajie; Liu, Keyi; Luo, Xukai; Jiang, Hua

doi:10.1631/jzus.b2200272

Cited by 12 publications

(7 citation statements)

References 62 publications

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“…When integrated with clinical characteristics, the model exhibited enhanced predictive efficacy compared to the standalone signature (Figure 5). Notably, among clinical characteristics integrated prognostic signatures, this signature exhibits a high AUC value of ROC curve, surpassing the predictive performance of both the endoplasmic reticulum stressrelated gene signature and the m6A-related lncRNA signature in OV [41,42]. In summary, the ubiquitin-related signature showed a satisfactory prognostic value for patients with OV.…”

Section: Advances Of the Ubrgs Signature For Prognostic Prediction In Ovmentioning

confidence: 87%

“…For instance, when examining endoplasmic reticulum stress-related genes in ovarian cancer across different datasets, variations may arise due to bias in samole selection. However, it is noteworthy that some overlap exists among these datasets [41,55]. To address this issue, additional experiments are required for validation.…”

Section: Potential Functions Of Fbxo9 In Ovmentioning

confidence: 99%

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Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

Luo,

Wang,

Zhang

et al. 2023

Biomolecules

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Background: Ovarian cancer (OV) is associated with high mortality and poses challenges in diagnosis and prognosis prediction. Ubiquitin-related genes (UbRGs) are involved in the initiation and progression of cancers, but have still not been utilized for diagnosis and prognosis of OV. Methods: K48-linked ubiquitination in ovarian tissues from our OV and control cohort was assessed using immunohistochemistry. UbRGs, including ubiquitin and ubiquitin-like regulators, were screened based on the TCGA-OV and GTEx database. Univariate Cox regression analysis identified survival-associated UbRGs. A risk model was established using the LASSO regression and multivariate Cox regression analysis. The relationship between UbRGs and immune cell infiltration, tumor mutational burden, drug sensitivity, and immune checkpoint was determined using the CIBERSORT, ESTIMATE, and Maftools algorithms, based on the Genomics of Drug Sensitivity in Cancer and TCGA-OV databases. GEPIA2.0 was used to analyze the correlation between FBXO9/UBD and DNA damage repair-related genes. Finally, FBXO9 and UBD were accessed in tissues or cells using immunohistochemistry, qPCR, and Western blot. Results: We confirmed the crucial role for ubiquitination in OV as a significant decrease of K48-linked ubiquitination was observed in primary OV lesions. We identified a prognostic signature utilizing two specific UbRGs, FBXO9 and UBD. The risk score obtained from this signature accurately predicted the overall survival of TCGA-OV training dataset and GSE32062 validation dataset. Furthermore, this risk score also showed association with immunocyte infiltration and drug sensitivity, revealing potential mechanisms for ubiquitination mediated OV risk. In addition, FBXO9, but not UBD, was found to be downregulated in OV and positively correlated with DNA damage repair pathways, suggesting FBXO9 as a potential cancer suppressor, likely via facilitating DNA damage repair. Conclusions: We identified and validated a signature of UbRGs that accurately predicts the prognosis, offers valuable guidance for optimizing chemotherapy and targeted therapies, and suggests a potential role for FBXO9 in OV.

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Section: Advances Of the Ubrgs Signature For Prognostic Prediction In Ovmentioning

confidence: 87%

Section: Potential Functions Of Fbxo9 In Ovmentioning

confidence: 99%

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

Luo,

Wang,

Zhang

et al. 2023

Biomolecules

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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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“…Studies have shown that ER stress may play an important role in the anticancer activity of proteasome inhibitors. ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic [53,54]. Some scholars observed the effect of proteasome inhibitor MG132 on OvCa cell line SKOV3 in vitro, and found that MG132 induced ER stress in SKOV3 cells, and the CHOP gene-mediated ER stress apoptotic pathway played an important role in the anti-OvCa activity of MG132 [55].…”

Section: Ovarian Cancermentioning

confidence: 99%

Research progress on the beneficial effects of exercise on endocrine system-related diseases in women by regulating ER stress pathways

Chen,

Zhang,

Sheng

et al. 2023

Preprint

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Exercise, as an effective non-drug intervention, plays an important role in preventing and alleviating several diseases. Endoplasmic reticulum (ER) stress is caused by an excessive accumulation of unfolded or misfolded proteins in the ER and also serves as the body’s internal self-protection mechanism. ER stress occurrence can be detected in the cells in many diseases such as cancer, diabetes, obesity, osteoporosis, neurodegenerative diseases, and metabolic diseases. In recent years, exercise has been suggested to change the molecular mechanisms related to various diseases by regulating ER stress. With increasing attention on women's health, some common diseases have also become research hotspots, such as breast, ovarian, cervical, endometrial cancer, polycystic ovary syndrome (PCOS) and endometriosis prevention and treatment; and other diseases. This manuscript reviews the relationship between exercise and ER stress and its role in common female endocrine system-related diseases.

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A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer

Cited by 12 publications

References 62 publications

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

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

Research progress on the beneficial effects of exercise on endocrine system-related diseases in women by regulating ER stress pathways

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