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Article ; Online: Overexpression of YAP confers radioresistance to esophageal cancer by altering the tumor microenvironment.

Yao, Guangyue / Shao, Mengqing / Nie, Yuanliu / Zhang, Wentao / Yang, Zhe / Li, Qiang

2024

Abstract: This study aimed to investigate the role of yes-associated protein (YAP) in the radiotherapy sensitivity of esophageal squamous cell carcinoma (ESCC). The clonogenic ability of ESCC cells was reduced after YAP silencing and radiotherapy. Overexpression ... ...

Abstract	This study aimed to investigate the role of yes-associated protein (YAP) in the radiotherapy sensitivity of esophageal squamous cell carcinoma (ESCC). The clonogenic ability of ESCC cells was reduced after YAP silencing and radiotherapy. Overexpression of YAP promoted cell survival and had a synergistic effect with the hypoxic microenvironment. YAP was found to directly regulate hypoxia-inducible factor 1α (HIF-1α). Bioinformatics analysis revealed the involvement of YAP in modulating the tumor immune microenvironment. Inhibition of YAP expression reduced myeloid-derived suppressor cells (MDSCs) and influenced the immunosuppressive state, leading to radio resistance. These findings provide insights into the YAP-HIF-1α interaction and support YAP as a potential target for enhancing radiotherapy sensitivity in esophageal cancer.
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.24122
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Article ; Online: Single-cell transcriptome sequencing analysis reveals intra-tumor heterogeneity in esophageal squamous cell carcinoma.

Nie, Yuanliu / Yao, Guangyue / Wei, Yanjun / Wu, Sheng / Zhang, Wentao / Xu, Xiaoying / Li, Qiang / Zhou, Fengge / Yang, Zhe

Environmental toxicology

2024

Abstract: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive system that poses a significant threat to human life and health. It is crucial to thoroughly investigate the mechanisms of esophageal carcinogenesis and identify ... ...

Abstract	Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive system that poses a significant threat to human life and health. It is crucial to thoroughly investigate the mechanisms of esophageal carcinogenesis and identify potential key molecular events in its carcinogenesis. Single-cell transcriptome sequencing is an emerging technology that has gained prominence in recent years for studying molecular mechanisms, which may help to further explore the underlying mechanisms of the ESCC tumor microenvironment in depth. The single-cell dataset was obtained from GSE160269 in the Gene Expression Omnibus database, including 60 tumor samples and four paracancer samples. The single-cell data underwent dimensional reduction clustering analysis to identify clusters and annotate expression profiles. Subcluster analysis was conducted for each cellular taxon. Copy number variation analysis of tumor cell subpopulations was performed to primarily identify malignant cells within them. A proposed chronological analysis was performed to obtain the process of cell differentiation. In addition, cell communication, transcription factor analysis, and tumor pathway analysis were also performed. Relevant risk models and key genes were established by univariate COX regression and LASSO analysis. The key genes obtained from the screen were subjected to appropriate silencing and cellular assays, including CCK-8, 5-ethynyl-2'-deoxyuridine, colony formation, and western blot. Single-cell analysis revealed that normal samples contained a large number of fibroblasts, T cells, and B cells, with fewer other cell types, whereas tumor samples exhibited a relatively balanced distribution of cell types. Subclassification analysis of immune cells, fibroblasts, endothelial cells, and epithelial cells revealed their specific spatial characteristics. The prognostic risk model, we constructed successfully, achieved accurate prognostic stratification for ESCC patients. The screened key gene, UPF3A, was found to be significantly associated with the development of ESCC by cellular assays. This process might be linked to the phosphorylation of ERK and P38. Single-cell transcriptome analysis successfully revealed the distribution of cell types and major expressed factors in ESCC patients, which could facilitate future in-depth studies on the therapeutic mechanisms of ESCC.
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.24243
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Article ; Online: A risk prognostic model for patients with esophageal squamous cell carcinoma basing on cuproptosis and ferroptosis.

Li, Jianan / Liu, Jixuan / Li, Jixian / Feng, Alei / Nie, Yuanliu / Yang, Zhe / Zhang, Wentao

Journal of cancer research and clinical oncology

2023 Volume 149, Issue 13, Page(s) 11647–11659

Abstract: Background: Cuproptosis, a form of copper-dependent programmed cell death recently presented by Tsvetkov et al., have been identified as a potential therapeutic target for refractory cancers and ferroptosis, a well-known form describing iron-dependent ... ...

Abstract	Background: Cuproptosis, a form of copper-dependent programmed cell death recently presented by Tsvetkov et al., have been identified as a potential therapeutic target for refractory cancers and ferroptosis, a well-known form describing iron-dependent cell death. However, whether the crossing of cuproptosis-related genes and ferroptosis-related genes can introduce some new idea, thus being used as a novel clinical and therapeutic predictor in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods: We collected ESCC patient data from the Gene Expression Omnibus and the Cancer Genome Atlas databases and used Gene Set Variation Analysis to score each sample based on cuproptosis and ferroptosis. We then performed weighted gene co-expression network analysis to identify cuproptosis and ferroptosis-related genes (CFRGs) and construct a ferroptosis and cuproptosis-related risk prognostic model, which we validated using a test group. We also investigated the relationship between the risk score and other molecular features, such as signaling pathways, immune infiltration, and mutation status. Results: Four CFRGs (MIDN, C15orf65, COMTD1 and RAP2B) were identified to construct our risk prognostic model. Patients were classified into low- and high-risk groups based on our risk prognostic model and the low-risk group showed significantly higher survival possibilities (P < 0.001). We used the "GO", "cibersort" and "ESTIMATE" methods to the above-mentioned genes to estimate the relationship among the risk score, correlated pathways, immune infiltration, and tumor purity. Conclusion: We constructed a prognostic model using four CFRGs and demonstrated its potential clinical and therapeutic guidance value for ESCC patients.
MeSH term(s)	Humans ; Esophageal Squamous Cell Carcinoma/genetics ; Prognosis ; Ferroptosis/genetics ; Esophageal Neoplasms/genetics ; Apoptosis ; rap GTP-Binding Proteins
Chemical Substances	RAP2B protein, human (EC 3.6.1.-) ; rap GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2023-07-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-023-05005-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Single-cell mapping of N6-methyladenosine in esophageal squamous cell carcinoma and exploration of the risk model for immune infiltration.

Nie, Yuanliu / Yao, Guangyue / Xu, Xiaoying / Liu, Yi / Yin, Ke / Lai, Jingjiang / Li, Qiang / Zhou, Fengge / Yang, Zhe

Frontiers in endocrinology

2023 Volume 14, Page(s) 1155009

Abstract: Background: N6-methyladenosine (m6A) modification is the most common RNA modification, but its potential role in the development of esophageal cancer and its specific mechanisms still need to be further investigated.: Methods: Bulk RNA-seq of 174 ... ...

Abstract	Background: N6-methyladenosine (m6A) modification is the most common RNA modification, but its potential role in the development of esophageal cancer and its specific mechanisms still need to be further investigated. Methods: Bulk RNA-seq of 174 patients with esophageal squamous carcinoma from the TCGA-ESCC cohort, GSE53625, and single-cell sequencing data from patients with esophageal squamous carcinoma from GSE188900 were included in this study. Single-cell analysis of scRNA-seq data from GSE188900 of 4 esophageal squamous carcinoma samples and calculation of PROGENy scores. Demonstrate the scoring of tumor-associated pathways for different cell populations. Cell Chat was calculated for cell populations. thereafter, m6A-related differential genes were sought and risk models were constructed to analyze the relevant biological functions and impact pathways of potential m6A genes and their impact on immune infiltration and tumor treatment sensitivity in ESCC was investigated. Results: By umap downscaling analysis, ESCC single-cell data were labelled into clusters of seven immune cell classes. Cellchat analysis showed that the network interactions of four signaling pathways, MIF, AFF, FN1 and CD99, all showed different cell type interactions. The prognostic risk model constructed by screening for m6A-related differential genes was of significant value in the prognostic stratification of ESCC patients and had a significant impact on immune infiltration and chemotherapy sensitivity in ESCC patients. Conclusion: In our study, we explored a blueprint for the distribution of single cells in ESCC based on m6A methylation and constructed a risk model for immune infiltration analysis and tumor efficacy stratification in ESCC on this basis. This may provide important potential guidance for revealing the role of m6A in immune escape and treatment resistance in esophageal cancer.
MeSH term(s)	Humans ; Esophageal Squamous Cell Carcinoma/genetics ; Esophageal Neoplasms/genetics ; Adenosine ; Cell Communication
Chemical Substances	Adenosine (K72T3FS567)
Language	English
Publishing date	2023-03-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1155009
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Article: Effects of Radiotherapy on Survival of Esophageal Cancer Patients Receiving Immunotherapy: Propensity Score Analysis and Nomogram Construction.

Nie, Yuanliu / Yao, Guangyue / Li, Liang / Feng, Alei / Zhang, Wentao / Xu, Xiaoying / Li, Qiang / Yang, Zhe

Cancer management and research

2022 Volume 14, Page(s) 2357–2371

Abstract: Purpose: The present study assessed the effects of radiotherapy on overall survival (OS) and progression-free survival time (PFS) in patients with stage II or higher esophageal cancer receiving immunotherapy; evaluated factors independently prognostic ... ...

Abstract	Purpose: The present study assessed the effects of radiotherapy on overall survival (OS) and progression-free survival time (PFS) in patients with stage II or higher esophageal cancer receiving immunotherapy; evaluated factors independently prognostic of OS and PFS in these patients; and utilized these factors to establish a prognostic nomogram. Patients and methods: This study enrolled 134 patients with stage II or higher esophageal cancer treated with chemotherapy (platinum-based agents plus paclitaxel or fluorouracil) and immunotherapy. These patients were divided into two groups, a radiotherapy (RT) group (n = 55) and a non-radiotherapy (non-RT) group (n = 79). Following 1:1 propensity score matching, OS and PFS were compared by the Kaplan-Meier method, and factors associated with survival were determined by univariate and multifactorial Cox regression analyses. These factors were used to construct a prognostic nomogram. Results: After propensity matching, all covariates were well balanced in the two groups (all P > 0.05). After matching, both median PFS (15.70 months [95% confidence interval (CI) 8.68-22.72 months] vs 5.70 months [95% CI 3.38-8.02 months], P = 0.002) and median OS (15.72 months [95% CI 12.94-18.46 months] vs 12.06 months [95% CI 9.91-14.20 months], P = 0.036) were significantly longer in the RT than in the non-RT group. Univariate and multifactorial analyses showed that RT, neutrophil-lymphocyte ratios, and tumor differentiation were independently prognostic of OS, with all hazard ratios (HRs) <1 and all P-values <0.05. A nomogram based on these factors was constructed, and its accuracy was verified. Conclusion: Immunotherapy plus RT resulted in better survival outcomes than immunotherapy alone. A nomogram based on prognostic factors can guide personalized treatment and monitor prognosis.
Language	English
Publishing date	2022-08-07
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2508013-1
ISSN	1179-1322
ISSN	1179-1322
DOI	10.2147/CMAR.S375821
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Article ; Online: Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma.

Zhang, Wentao / Qu, Haizeng / Ma, Xiaoqing / Li, Liang / Wei, Yanjun / Wang, Ye / Zeng, Renya / Nie, Yuanliu / Zhang, Chenggui / Yin, Ke / Zhou, Fengge / Yang, Zhe

Frontiers in immunology

2023 Volume 14, Page(s) 1179742

Abstract: Background: Cuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in ... ...

Abstract	Background: Cuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in cancer progression and patient prognosis. Therefore, our study aimed to create a survival prediction model for lung adenocarcinoma patients based on cuproptosis and immune-related genes. This model can be utilized to enhance personalized treatment for patients. Methods: RNA sequencing (RNA-seq) data of lung adenocarcinoma (LUAD) patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The levels of immune cell infiltration in the GSE68465 cohort were determined using gene set variation analysis (GSVA), and immune-related genes (IRGs) were identified using weighted gene coexpression network analysis (WGCNA). Additionally, cuproptosis-related genes (CRGs) were identified using unsupervised clustering. Univariate COX regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were performed to develop a risk prognostic model for cuproptosis and immune-related genes (CIRGs), which was subsequently validated. Various algorithms were utilized to explore the relationship between risk scores and immune infiltration levels, and model genes were analyzed based on single-cell sequencing. Finally, the expression of signature genes was confirmed through quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB). Results: We have identified 5 Oncogenic Driver Genes namely CD79B, PEBP1, PTK2B, STXBP1, and ZNF671, and developed proportional hazards regression models. The results of the study indicate significantly reduced survival rates in both the training and validation sets among the high-risk group. Additionally, the high-risk group displayed lower levels of immune cell infiltration and expression of immune checkpoint compared to the low-risk group.
MeSH term(s)	Humans ; Prognosis ; Adenocarcinoma of Lung/genetics ; Algorithms ; Apoptosis ; Lung Neoplasms/genetics ; Tumor Suppressor Proteins
Chemical Substances	ZNF671 protein, human ; Tumor Suppressor Proteins
Language	English
Publishing date	2023-08-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1179742
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Leveraging a disulfidptosis-related signature to predict the prognosis and immunotherapy effectiveness of cutaneous melanoma based on machine learning.

Zhao, Yi / Wei, Yanjun / Fan, Lingjia / Nie, Yuanliu / Li, Jianan / Zeng, Renya / Li, Jixian / Zhan, Xiang / Lei, Lingli / Kang, Zhichao / Li, Jiaxin / Zhang, Wentao / Yang, Zhe

Molecular medicine (Cambridge, Mass.)

2023 Volume 29, Issue 1, Page(s) 145

Abstract: Background: Disulfidptosis is a recently discovered programmed cell death pathway. However, the exact molecular mechanism of disulfidptosis in cutaneous melanoma remains unclear.: Methods: In this study, clustering analysis was performed using data ... ...

Abstract	Background: Disulfidptosis is a recently discovered programmed cell death pathway. However, the exact molecular mechanism of disulfidptosis in cutaneous melanoma remains unclear. Methods: In this study, clustering analysis was performed using data from public databases to construct a prognostic model, which was subsequently externally validated. The biological functions of the model genes were then investigated through various experimental techniques, including qRT-PCR, Western blotting, CCK-8 assay, wound healing assay, and Transwell assay. Results: We constructed a signature using cutaneous melanoma (CM) data, which accurately predicts the overall survival (OS) of patients. The predictive value of this signature for prognosis and immune therapy response was validated using multiple external datasets. High-risk CM subgroups may exhibit decreased survival rates, alterations in the tumor microenvironment (TME), and increased tumor mutation burden. We initially verified the expression levels of five optimum disulfidptosis-related genes (ODRGs) in normal tissues and CM. The expression levels of these genes were further confirmed in HaCaT cells and three melanoma cell lines using qPCR and protein blotting analysis. HLA-DQA1 emerged as the gene with the highest regression coefficient in our risk model, highlighting its role in CM. Mechanistically, HLA-DQA1 demonstrated the ability to suppress CM cell growth, proliferation, and migration. Conclusion: In this study, a novel signature related to disulfidptosis was constructed, which accurately predicts the survival rate and treatment sensitivity of CM patients. Additionally, HLA-DQA1 is expected to be a feasible therapeutic target for effective clinical treatment of CM.
MeSH term(s)	Humans ; Melanoma/genetics ; Melanoma/therapy ; Skin Neoplasms/genetics ; Skin Neoplasms/therapy ; Immunotherapy ; Machine Learning ; Tumor Microenvironment/genetics ; Melanoma, Cutaneous Malignant
Language	English
Publishing date	2023-10-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283676-x
ISSN	1528-3658 ; 1076-1551
ISSN (online)	1528-3658
ISSN	1076-1551
DOI	10.1186/s10020-023-00739-x
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Article ; Online: Overexpression of YAP confers radioresistance to esophageal cancer by altering the tumor microenvironment.

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Article ; Online: Single-cell transcriptome sequencing analysis reveals intra-tumor heterogeneity in esophageal squamous cell carcinoma.

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Article ; Online: A risk prognostic model for patients with esophageal squamous cell carcinoma basing on cuproptosis and ferroptosis.

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Article: Single-cell mapping of N6-methyladenosine in esophageal squamous cell carcinoma and exploration of the risk model for immune infiltration.

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Article: Effects of Radiotherapy on Survival of Esophageal Cancer Patients Receiving Immunotherapy: Propensity Score Analysis and Nomogram Construction.

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Article ; Online: Identification of cuproptosis and immune-related gene prognostic signature in lung adenocarcinoma.

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Article ; Online: Leveraging a disulfidptosis-related signature to predict the prognosis and immunotherapy effectiveness of cutaneous melanoma based on machine learning.

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