Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

Zhang, Yuke; Song, Yancheng; Dai, Jiangwen; Wang, Zhaoxiang; Zeng, Yu-Hao; Chen, Feng; Zhang, Peng

doi:10.3389/fphar.2022.909123

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…This finding demonstrated that ER stress was suppressed in such patients. 50 The collective observations from previous works, further confirm our conclusion that the anticancer effect of ATF3 is likely mediated through the regulation of the apoptotic signaling pathway in response to ER stress in ccRCC.…”

Section: Discussionsupporting

confidence: 80%

Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression

Yang,

Hou,

et al. 2024

Int J Immunopathol Pharmacol

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Background: Clear cell renal cell carcinoma (ccRCC) is the most invasive type of cancer, with a high risk of metastasis and recurrence. Therefore, there is an urgent need to identify novel prognostic predictors and therapeutic targets of ccRCC. Activating transcription factor 3 (ATF3), a tumor oncogene or repressor, has rarely been examined in ccRCC. In the present study, we comprehensively elucidate the prognostic value and potential functions of ATF3 in ccRCC. Methods: Several TCGA-based online databases were used to analyze ATF3 expression in ccRCC and determine ccRCC prognosis. The upstream-binding micro (mi) RNAs of ATF3 and long non-coding (lnc)RNAs were predicted using the StarBase database. Results: Analysis of several TCGA-based online databases showed that ATF3 expression is decreased in ccRCC, suggesting a significant association with the prognosis of patients with ccRCC. Furthermore, we found hsa-miR-221-3p to be potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of the upstream lncRNAs indicated that PAXIP1-AS2 and OIP5-AS1 were the most potent upstream lncRNAs of the hsa-miR-221-3p/ATF3 axis in ccRCC. The results of the GO and KEGG analyses implied that ATF3 is likely involved in the regulation of apoptotic signaling in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis revealed a positive relationship between ATF3 expression and ER stress. Conclusions: Our in silico findings highlighted that ATF3 expression was low in ccRCC and negatively correlated with poor prognosis. Furthermore, PAXIP1-AS2 and the OIP5-AS1/hsa-miR-221-3p/ATF3 axis were identified as significant potential regulators of ER stress-mediated apoptosis in ccRCC.

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Section: Discussionsupporting

confidence: 80%

Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression

Yang,

Hou,

et al. 2024

Int J Immunopathol Pharmacol

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“…And another study found that the expression of ATF6, PERK, but not IRE1α, was downregulated in ccRCC patients with advanced tumor stage and grade. This demonstrated ER stress was suppressed in progressive ccRCC patients 43 . The above studies further con rm our conclusion anticancer effect of ATF3 may be achieved through the regulation of apoptotic signaling pathway in response to ER stress in ccRCC.…”

Section: Discussionmentioning

confidence: 89%

Down-regulated ATF3 Promotes Renal Clear Cell Carcinoma Progression Through PAXIP1-AS2 and OIP5-AS1/ hsa-miR-221-3p/ATF3 Axis Regulation of Endoplasmic Reticulum Stress

Yang

Hou

et al. 2023

Preprint

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Clear cell renal cell carcinoma (ccRCC) is the most invasive type with high metastasis risk and high recurrence rate in renal cell carcinoma and there is a pressing need to explore novel prognostic predictors and therapeutic targets for ccRCC. Activating transcription factor 3 (ATF3), an oncogene or a suppressor for tumor, has been poorly reported in ccRCC. Here, we comprehensively clarified the prognostic value and potential function of ATF3 in ccRCC. By analyzing ATF3 in ccRCC several TCGA-based online databases, we found that ATF3 expression is decreased in ccRCC and indicate that ATF3 is significantly associated with the prognosis of ccRCC patients. hsa-miR-221-3p might be the most potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of upstream lncRNAs showed PAXIP1-AS2 and OIP5-AS1 might be the most potential upstream lncRNAs of hsa-miR-221-3p/ATF3 axis in ccRCC. GO and KEGG results implied that ATF3 is involved in the regulation of apoptotic signaling pathway in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis showed a positive correlation between ATF3 and ER stress. According to present study, down-regulated ATF3 promotes renal clear cell carcinoma progression through PAXIP1-AS2 and OIP5-AS1/ hsa-miR-221-3p/ATF3 axis regulation of endoplasmic reticulum stress.

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“…In the case of hepatocellular carcinoma, the prediction model based on endoplasmic reticulum-related genes showed superior performance (26,27). A surprising association was also found between endoplasmic reticulum stress-related genes and drug therapy in Clear cell renal cell carcinoma (28). Therefore, UCEC patients' prognosis was affected by the endoplasmic reticulum stress-related gene IncRNA signature as well.…”

Section: Discussionmentioning

confidence: 97%

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma

Shen

Yang

2023

Front. Oncol.

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BackgroundEndoplasmic reticulum (ER) stress is closely related to the occurrence, development and treatment of tumors. Recent studies suggest ER stress as a therapeutic strategy of choice for cancer. However, ER stress-related long non-coding RNA (lncRNA) predictive value in endometrial carcinoma (UCEC) remains to be further evaluated. The purpose of this study was to establish relies on the signature of ER stress-related lncRNA forecast to predict the prognosis of patients with UCEC.MethodsWe downloaded the RNA expression profile dataset and matched clinical data from the Cancer Genome Atlas (TCGA) database, and applied univariate and multivariate Cox regression analysis to build predictive signature. Kaplan-meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Gene set enrichment analysis (GSEA) was used to study the functional characteristics. Single sample Gene set enrichment analysis (ssGSEA) was used to analyze the relationship between immune status and predicted signature. Correlations between the potential usefulness of treatment for UCEC patients and predictive signature were also analyzed.ResultsWe established a signature composed of eight ER stress-related lncRNAs (MIR34AHG, AC073842.2, PINK1AS, AC024909.2, MIR31HG, AC007422.2, AC061992.1, AC003102.1). The signature of ER stress-related lncRNA provided better diagnostic value compared with age and tumor grade, and the area under the receiver operating curve was 0.788. The overall and disease-free survival probability of patients in the high-risk group is lower than that in the low-risk group. GSEA indicated that the pathways were mainly enriched for cancer, immunity and reproduction related pathways. ss-GSEA shows that prediction signature and activation of dendritic cells, immature dendritic cells, T helper cells and immune status of the Treg are significantly related. High-risk groups may against PD - 1/L1 immunotherapy and JNK inhibitors VIII, Z.LLNle.CHO, DMOG and JNK. 9 l more sensitive.ConclusionThe ER stress signature can independently predict the prognosis of UCEC patients, and provide guidance for conventional chemotherapy and immunotherapy of UCEC patients.

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Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

Cited by 8 publications

References 51 publications

Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression

Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression

Down-regulated ATF3 Promotes Renal Clear Cell Carcinoma Progression Through PAXIP1-AS2 and OIP5-AS1/ hsa-miR-221-3p/ATF3 Axis Regulation of Endoplasmic Reticulum Stress

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma

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