Identification of the Prognostic Value of Tumor Microenvironment-Related Genes in Esophageal Squamous Cell Carcinoma

Zhang, Donglei; Qian, Chenyin; Wei, Huabing; Qian, Xiaozhe

doi:10.3389/fmolb.2020.599475

Cited by 24 publications

(22 citation statements)

References 34 publications

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“…MXRA8 is reported to confer debilitating acute and chronic musculoskeletal disease, since it serves as an entry mediator for multiple arthritogenic alphaviruses ( 15 ). In terms of tumor progression, several studies have reported that high expressions of MXRA8 had poor overall survival (OS) in kidney renal clear cell carcinoma patients and is correlated with tumor microenvironment in esophageal squamous cell carcinoma ( 16 ). However, the underlying functions of MXRA8 in gliomas have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Matrix Remodeling-Associated Protein 8 as a Novel Indicator Contributing to Glioma Immune Response by Regulating Ferroptosis

Chen

Song

et al. 2022

Front. Immunol.

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Glioma is a highly malignant brain tumor with a poor survival rate. Novel biomarkers that act as prompt indicators of glioma are urgently needed. In this study, we identified and validated prognosis-related differentially expressed genes by datasets of glioma in the GEO and TCGA databases. Ferroptosis is a newly recognized process of cell death playing a vital role in cancer biology. Pearson correlation coefficient were used to discovery the prognosis-related genes which have the highest correlation with ferroptosis. Matrix remodeling-associated protein 8 (MXRA8) was identified as a novel prognosis indicator which may be involved in ferroptosis. The expression of MXRA8 was significantly higher in glioma compared with normal brain tissue, and increased expression of MXRA8 was associated with unfavorable survivals. Furthermore, in vitro analysis showed that knockdown of MXRA8 inhibited the cell viability in T98G and U251 cells and increased the sensitivity of glioma cells to temozolomide. We further observed that downregulation of MXRA8 elevated the levels of intracellular ferrous iron and lipid peroxidation, accompanied by upregulation of NCOA4 and suppression of FTH1. Moreover, co-expression analyses showed that GO term and KEGG pathways were mainly enriched in immunity-related pathways, such as neutrophil-related immunity, adaptive immune response, and cytokine binding. Through ssGSEA algorithm and TISIDB database, immunological analyses showed that MXRA8 was significantly correlated with various immune infiltration cells including NK cells, macrophages, and neutrophils. Meanwhile, MXRA8 was also associated with chemokines and multiple immunoinhibitory molecules, such as TGF-β1, IL-10, PD-L1, and CTLA4. We also found that MXRA8 was positively associated with immune infiltration score, and patients with higher immune score underwent worse overall survivals. Moreover, IHC staining indicated a highly positive correlation of MXRA8 with a macrophage marker CSF1R. The co-cultured models of glioma cells and M2 macrophages showed MXRA8 knockdown glioma cells alleviated the infiltration of M2 macrophage, while the reduced M2 macrophage infiltration generated by MXRA8 could be rescued by Fer-1 treatment. These results suggest that MXRA8 promotes glioma progression and highlight the pivotal role of MXRA8 in ferroptosis and immune microenvironment of glioma. Therefore, MXRA8 may serve as a novel prognostic marker and therapeutic target for glioma.

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Section: Introductionmentioning

confidence: 99%

Matrix Remodeling-Associated Protein 8 as a Novel Indicator Contributing to Glioma Immune Response by Regulating Ferroptosis

Chen

Song

et al. 2022

Front. Immunol.

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“…CELF4, one of the CELF protein family, which belongs to a group of splicing regulators that controls developmentally regulated and tissue-specific splicing events [ 28 ]. SLC24A2, a potassium-dependent sodium-calcium exchanger, were observed in pancreatic ductal adenocarcinoma and were associated with esophageal squamous cell carcinoma prognosis [ 29 ]. TRIM67 was involved in neuroprotective effects and tumor processes, has been reported as a potential target to inhibit CRC metastasis [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic stemness biomarkers in colon adenocarcinoma drug resistance

Chen

Zhu

et al. 2022

BMC Genom Data

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Background Colon adenocarcinoma (COAD) is one of the leading causes of death worldwide. Cancer stem cells (CSCs) are vital for COAD chemoresistance and recurrence, however little is known about stem cell-related biomarkers in drug resistance and COAD prognosis prediction. Methods To uncover the roles of CSC in COAD tumorigenesis, chemoresistance, and prognosis, we retrieved COAD patients’ RNAseq data from TCGA (The Cancer Genome Atlas). We further performed analysis of differentially expressed genes (DEGs) and mRNA expression-based stemness index (mRNAsi) to identify stemness-related COAD biomarkers. We then evaluated the roles of mRNAsi in tumorigenesis, clinical-stage, overall survival (OS), and chemoresistance. Afterward, we used identified prognostic stemness-related genes (PSRGs) to construct a prediction model. After constructing the prediction model, we used elastic Net regression and area under the curve (AUC) to explore the prediction value of PSRGs based on risk scores and the receiver operator characteristic (ROC) curve. To elucidate the underlying interconnected systems, we examined relationships between the levels of TFs, PSRGs, and 50 cancer hallmarks by a Pearson correlation analysis. Results Twelve thousand one hundred eight DEGs were identified by comparing 456 primary COADs and 41 normal solid tissue samples. Furthermore, we identified 4351 clinical stage-related DEGs, 16,516 stemness-associated DEGs, and 54 chemoresistance-related DEGs from cancer stages: mRNAsi, and COAD chemoresistance. Compared to normal tissue samples, mRNAsi in COAD patients were marked on an elevation and involved in prognosis (p = 0.027), stemness-related DEGs based on chemoresistance (OR = 3.28, p ≤ 0.001) and AJCC clinical stage relating (OR = 4.02, p ≤ 0.001) to COAD patients. The prediction model of prognosis were constructed using the 6 PSRGs with high accuracy (AUC: 0.659). The model identified universal correlation between NRIP2 and FDFT1 (key PRSGs), and some cancer related transcription factors (TFs) and trademarks of cancer gene were in the regulatory network. Conclusion We found that mRNAsi is a reliable predictive biomarker of tumorigenesis and COAD prognosis. Our established prediction model of COAD chemoresistance, which includes the six PSRGs, is effective, as the model provides promising therapeutic targets in the COAD.

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“…ESCC is the prevalent histological subtype of esophageal cancer, with a poor prognosis and prone to distant metastasis [ 3 , 27 ]. Therefore, exploring potential biomarkers is essential for managing and predicting the prognosis of ESCC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of Epithelial-Mesenchymal Transition- (EMT-) Related LncRNA for Prognostic Prediction and Risk Stratification in Esophageal Squamous Cell Carcinoma

et al. 2021

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Background. Epithelial-mesenchymal transition (EMT) is significantly associated with the invasion and development of esophageal squamous cell carcinoma (ESCC). However, the importance of EMT-related long noncoding RNA (lncRNA) is little known in ESCC. Methods. GSE53624 ( N = 119 ) and GSE53622 ( N = 60 ) datasets retrieved from the Gene Expression Omnibus (GEO) database were used as training and external validation cohorts, respectively. GSE53624 and GSE53622 datasets were all sampled from China. Then, the prognostic value of EMT-related lncRNA was comprehensively investigated by weighted coexpression network analysis (WGCNA) and COX regression model. Results. High expression of PLA2G4E-AS1, AC063976.1, and LINC01592 significantly correlated with the favorable overall survival (OS) of ESCC patients, and LINC01592 had the greatest contribution to OS. Importantly, ESCC patients were divided into low- and high-risk groups based on the optimal cut-off value of risk score estimated by the multivariate COX regression model of these three lncRNA. Patients with high risk had a shorter OS rate and restricted mean survival time (RMST) than those with low risk. Moreover, univariate and multivariate COX regression revealed that risk stratification, age, and TNM were independent prognostic predictors, which were used to construct a nomogram model for individualized and visualized prognosis prediction of ESCC patients. The calibration curves and time-dependent ROC curves in the training and validation cohorts suggested that the nomogram model had a good performance. Interestingly, clear trends indicated that risk score positively correlated with tumor microenvironment (TME) scores and immune checkpoints TIGIT, CTLA4, and BTLA. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that PLA2G4E-AS1, AC063976.1, and LINC01592 were primarily associated with TNF signaling pathway, NF-kappa B signaling pathway, and ECM-receptor interaction. Conclusion. We developed EMT-related lncRNA PLA2G4E-AS1, AC063976.1, and LINC01592 for prognostic prediction and risk stratification of Chinese ESCC patients, which might provide deep insight for personalized prognosis prediction in Chinese ESCC patients and be potential biomarkers for designing novel therapy.

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Identification of the Prognostic Value of Tumor Microenvironment-Related Genes in Esophageal Squamous Cell Carcinoma

Cited by 24 publications

References 34 publications

Matrix Remodeling-Associated Protein 8 as a Novel Indicator Contributing to Glioma Immune Response by Regulating Ferroptosis

Matrix Remodeling-Associated Protein 8 as a Novel Indicator Contributing to Glioma Immune Response by Regulating Ferroptosis

Identification of prognostic stemness biomarkers in colon adenocarcinoma drug resistance

Identification of Epithelial-Mesenchymal Transition- (EMT-) Related LncRNA for Prognostic Prediction and Risk Stratification in Esophageal Squamous Cell Carcinoma

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