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Article ; Online: Fascin lysine 471 acetylation cooperates with serine 39 phosphorylation to inhibit actin-bundling activity and tumor metastasis in esophageal squamous cell carcinoma.

Zeng, Fa-Min / Cheng, Yin-Wei / He, Jian-Zhong / Xu, Xiu-E / Liao, Lian-Di / Xu, Li-Yan / Li, En-Min

Cancer communications (London, England)

2022 Volume 42, Issue 7, Page(s) 668–672

MeSH term(s)	Acetylation ; Actins/metabolism ; Carrier Proteins ; Esophageal Neoplasms/pathology ; Esophageal Squamous Cell Carcinoma ; Humans ; Lysine ; Microfilament Proteins ; Phosphorylation ; Serine/metabolism
Chemical Substances	Actins ; Carrier Proteins ; Microfilament Proteins ; fascin (146808-54-0) ; Serine (452VLY9402) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2022-05-06
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ISSN	2523-3548
ISSN (online)	2523-3548
DOI	10.1002/cac2.12297
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Article ; Online: Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer.

He, Jian-Zhong / Chen, Yang / Zeng, Fa-Min / Huang, Qing-Feng / Zhang, Hai-Feng / Wang, Shao-Hong / Yu, Shuai-Xia / Pang, Xiao-Xiao / Liu, Ye / Xu, Xiu-E / Wu, Jian-Yi / Shen, Wen-Jun / Li, Zhan-Yu / Li, En-Min / Xu, Li-Yan

Journal of experimental & clinical cancer research : CR

2023 Volume 42, Issue 1, Page(s) 136

Abstract: Background: Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is ... ...

Abstract	Background: Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC). Methods: Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages. Results: We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA) Conclusions: Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.
MeSH term(s)	Humans ; Esophageal Neoplasms/metabolism ; Esophageal Squamous Cell Carcinoma/pathology ; Carcinoma, Squamous Cell/pathology ; CD8-Positive T-Lymphocytes/metabolism ; Prognosis ; Fibroblasts/metabolism ; Tumor Microenvironment
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-023-02697-y
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Article ; Online: SARS‐CoV‐2 spike spurs intestinal inflammation via VEGF production in enterocytes

Fa‐Min Zeng / Ying‐wen Li / Zhao‐hua Deng / Jian‐zhong He / Wei Li / Lijie Wang / Ting Lyu / Zhanyu Li / Chaoming Mei / Meiling Yang / Yingying Dong / Guan‐Min Jiang / Xiaofeng Li / Xi Huang / Fei Xiao / Ye Liu / Hong Shan / Huanhuan He

EMBO Molecular Medicine, Vol 14, Iss 5, Pp n/a-n/a (2022)

2022

Abstract: Abstract Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID‐19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID‐19. ... ...

Abstract	Abstract Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID‐19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID‐19. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS‐CoV‐2 spike protein, we further revealed that VEGF was over‐produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS‐CoV‐2 spike promoted VEGF production through activating the Ras‐Raf‐MEK‐ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID‐19.
Keywords	COVID‐19 ; GI symptoms ; intestinal inflammation ; vascular permeability ; VEGF ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article ; Online: SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes.

Zeng, Fa-Min / Li, Ying-Wen / Deng, Zhao-Hua / He, Jian-Zhong / Li, Wei / Wang, Lijie / Lyu, Ting / Li, Zhanyu / Mei, Chaoming / Yang, Meiling / Dong, Yingying / Jiang, Guan-Min / Li, Xiaofeng / Huang, Xi / Xiao, Fei / Liu, Ye / Shan, Hong / He, Huanhuan

EMBO molecular medicine

2022 Volume 14, Issue 5, Page(s) e14844

Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. Plasma VEGF ... ...

Abstract	Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS-CoV-2 spike protein, we further revealed that VEGF was over-produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS-CoV-2 spike promoted VEGF production through activating the Ras-Raf-MEK-ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID-19.
MeSH term(s)	Animals ; COVID-19 ; Enterocytes/metabolism ; Humans ; Inflammation/metabolism ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vascular Endothelial Growth Factor A
Chemical Substances	Spike Glycoprotein, Coronavirus ; Vascular Endothelial Growth Factor A ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.202114844
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Article ; Online: A Novel Three-Gene Model Predicts Prognosis and Therapeutic Sensitivity in Esophageal Squamous Cell Carcinoma.

Zeng, Fa-Min / He, Jian-Zhong / Wang, Shao-Hong / Liu, De-Kai / Xu, Xiu-E / Wu, Jian-Yi / Li, En-Min / Xu, Li-Yan

BioMed research international

2019 Volume 2019, Page(s) 9828637

Abstract: To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have ...

Abstract	To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have superiority over the use of single biomarkers. Our previous studies have identified the crucial role of ezrin in ESCC progression, which prompted us to hypothesize that ezrin-associated proteins contribute to the pathobiology of ESCC. Herein, we explored the clinical value of a molecular model constructed based on ezrin-associated proteins in ESCC patients. We revealed that the ezrin-associated proteins (MYC, PDIA3, and ITGA5B1) correlated with the overall survival (OS) and disease-free survival (DFS) of patients with ESCC. High expression of MYC was associated with advanced pTNM-stage (
MeSH term(s)	Biomarkers, Tumor/genetics ; Esophageal Squamous Cell Carcinoma/diagnosis ; Esophageal Squamous Cell Carcinoma/drug therapy ; Esophageal Squamous Cell Carcinoma/genetics ; Esophageal Squamous Cell Carcinoma/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Models, Genetic ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Predictive Value of Tests ; Prognosis
Chemical Substances	Biomarkers, Tumor ; Neoplasm Proteins
Language	English
Publishing date	2019-11-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2019/9828637
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Article: Promotion of rs3746804 (p. L267P) polymorphism to intracellular SLC52A3a trafficking and riboflavin transportation in esophageal cancer cells

Long, Lin / Pang, Xiao-Xiao / Zeng, Fa-Min / Zhan, Xiu-Hui / Xie, Ying-Hua / Pan, Feng / Wang, Wei / Liao, Lian-Di / Xu, Xiu-E. / Li, Bin / Wang, Li-Dong / Chang, Zhi-Jie / Li, En-Min / Xu, Li-Yan

Amino acids. 2021 Aug., v. 53, no. 8

2021

Abstract: Riboflavin is an essential micronutrient for normal cellular growth and function. Lack of dietary riboflavin is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). Previous studies have identified that the human riboflavin ... ...

Abstract	Riboflavin is an essential micronutrient for normal cellular growth and function. Lack of dietary riboflavin is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). Previous studies have identified that the human riboflavin transporter SLC52A3a isoform (encoded by SLC52A3) plays a prominent role in esophageal cancer cell riboflavin transportation. Furthermore, SLC52A3 gene single nucleotide polymorphisms rs3746804 (T>C, L267P) and rs3746803 (C >T, T278M) are associated with ESCC risk. However, whether SLC52A3a (p.L267P) and (p.T278M) act in riboflavin transportation in esophageal cancer cell remains inconclusive. Here, we constructed the full-length SLC52A3a protein fused to green fluorescent protein (GFP-SLC52A3a-WT and mutants L267P, T278M, and L267P/T278M). It was confirmed by immunofluorescence-based confocal microscopy that SLC52A3a-WT, L267P, T278M, and L267P/T278M expressed in cell membrane, as well as in a variety of intracellular punctate structures. The live cell confocal imaging showed that SLC52A3a-L267P and L267P/T278M increased the intracellular trafficking of SLC52A3a in ESCC cells. Fluorescence recovery after photobleaching of GFP-tagged SLC52A3a meant that intracellular trafficking of SLC52A3a-L267P and L267P/T278M was rapid dynamics process, leading to its stronger ability to transport riboflavin. Taken together, the above results indicated that the rs3746804 (p.L267P) polymorphism promoted intracellular trafficking of SLC52A3a and riboflavin transportation in ESCC cells.
Keywords	cell growth ; cell membranes ; confocal microscopy ; esophageal neoplasms ; fluorescence recovery after photobleaching ; genes ; green fluorescent protein ; humans ; neoplasm cells ; riboflavin ; risk ; squamous cell carcinoma ; transportation
Language	English
Dates of publication	2021-08
Size	p. 1197-1209.
Publishing place	Springer Vienna
Document type	Article
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-021-03025-4
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 3490: Show issues

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Article ; Online: Promotion of rs3746804 (p. L267P) polymorphism to intracellular SLC52A3a trafficking and riboflavin transportation in esophageal cancer cells.

Long, Lin / Pang, Xiao-Xiao / Zeng, Fa-Min / Zhan, Xiu-Hui / Xie, Ying-Hua / Pan, Feng / Wang, Wei / Liao, Lian-Di / Xu, Xiu-E / Li, Bin / Wang, Li-Dong / Chang, Zhi-Jie / Li, En-Min / Xu, Li-Yan

Amino acids

2021 Volume 53, Issue 8, Page(s) 1197–1209

Abstract	Riboflavin is an essential micronutrient for normal cellular growth and function. Lack of dietary riboflavin is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). Previous studies have identified that the human riboflavin transporter SLC52A3a isoform (encoded by SLC52A3) plays a prominent role in esophageal cancer cell riboflavin transportation. Furthermore, SLC52A3 gene single nucleotide polymorphisms rs3746804 (T>C, L267P) and rs3746803 (C >T, T278M) are associated with ESCC risk. However, whether SLC52A3a (p.L267P) and (p.T278M) act in riboflavin transportation in esophageal cancer cell remains inconclusive. Here, we constructed the full-length SLC52A3a protein fused to green fluorescent protein (GFP-SLC52A3a-WT and mutants L267P, T278M, and L267P/T278M). It was confirmed by immunofluorescence-based confocal microscopy that SLC52A3a-WT, L267P, T278M, and L267P/T278M expressed in cell membrane, as well as in a variety of intracellular punctate structures. The live cell confocal imaging showed that SLC52A3a-L267P and L267P/T278M increased the intracellular trafficking of SLC52A3a in ESCC cells. Fluorescence recovery after photobleaching of GFP-tagged SLC52A3a meant that intracellular trafficking of SLC52A3a-L267P and L267P/T278M was rapid dynamics process, leading to its stronger ability to transport riboflavin. Taken together, the above results indicated that the rs3746804 (p.L267P) polymorphism promoted intracellular trafficking of SLC52A3a and riboflavin transportation in ESCC cells.
MeSH term(s)	Biological Transport ; Cell Line, Tumor ; Esophageal Neoplasms/metabolism ; Esophageal Neoplasms/pathology ; Esophageal Squamous Cell Carcinoma/metabolism ; Esophageal Squamous Cell Carcinoma/pathology ; Exome ; Green Fluorescent Proteins/genetics ; Humans ; Membrane Transport Proteins/genetics ; Polymerase Chain Reaction/methods ; Polymorphism, Single Nucleotide ; Riboflavin/metabolism
Chemical Substances	Membrane Transport Proteins ; SLC52A3 protein, human ; Green Fluorescent Proteins (147336-22-9) ; Riboflavin (TLM2976OFR)
Language	English
Publishing date	2021-07-05
Publishing country	Austria
Document type	Journal Article
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-021-03025-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: FSCC: Few-Shot Learning for Macromolecule Classification Based on Contrastive Learning and Distribution Calibration in Cryo-Electron Tomography.

Gao, Shan / Zeng, Xiangrui / Xu, Min / Zhang, Fa

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 931949

Abstract: Cryo-electron tomography (Cryo-ET) is an emerging technology for three-dimensional (3D) visualization of macromolecular structures in the near-native state. To recover structures of macromolecules, millions of diverse macromolecules captured in tomograms ...

Abstract	Cryo-electron tomography (Cryo-ET) is an emerging technology for three-dimensional (3D) visualization of macromolecular structures in the near-native state. To recover structures of macromolecules, millions of diverse macromolecules captured in tomograms should be accurately classified into structurally homogeneous subsets. Although existing supervised deep learning-based methods have improved classification accuracy, such trained models have limited ability to classify novel macromolecules that are unseen in the training stage. To adapt the trained model to the macromolecule classification of a novel class, massive labeled macromolecules of the novel class are needed. However, data labeling is very time-consuming and labor-intensive. In this work, we propose a novel few-shot learning method for the classification of novel macromolecules (named FSCC). A two-stage training strategy is designed in FSCC to enhance the generalization ability of the model to novel macromolecules. First, FSCC uses contrastive learning to pre-train the model on a sufficient number of labeled macromolecules. Second, FSCC uses distribution calibration to re-train the classifier, enabling the model to classify macromolecules of novel classes (unseen class in the pre-training). Distribution calibration transfers learned knowledge in the pre-training stage to novel macromolecules with limited labeled macromolecules of novel class. Experiments were performed on both synthetic and real datasets. On the synthetic datasets, compared with the state-of-the-art (SOTA) method based on supervised deep learning, FSCC achieves competitive performance. To achieve such performance, FSCC only needs five labeled macromolecules per novel class. However, the SOTA method needs 1100 ∼ 1500 labeled macromolecules per novel class. On the real datasets, FSCC improves the accuracy by 5% ∼ 16% when compared to the baseline model. These demonstrate good generalization ability of contrastive learning and calibration distribution to classify novel macromolecules with very few labeled macromolecules.
Language	English
Publishing date	2022-07-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.931949
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Article ; Online: FSCC

Shan Gao / Xiangrui Zeng / Min Xu / Fa Zhang

Frontiers in Molecular Biosciences, Vol

Few-Shot Learning for Macromolecule Classification Based on Contrastive Learning and Distribution Calibration in Cryo-Electron Tomography

2022 Volume 9

Abstract	Cryo-electron tomography (Cryo-ET) is an emerging technology for three-dimensional (3D) visualization of macromolecular structures in the near-native state. To recover structures of macromolecules, millions of diverse macromolecules captured in tomograms should be accurately classified into structurally homogeneous subsets. Although existing supervised deep learning–based methods have improved classification accuracy, such trained models have limited ability to classify novel macromolecules that are unseen in the training stage. To adapt the trained model to the macromolecule classification of a novel class, massive labeled macromolecules of the novel class are needed. However, data labeling is very time-consuming and labor-intensive. In this work, we propose a novel few-shot learning method for the classification of novel macromolecules (named FSCC). A two-stage training strategy is designed in FSCC to enhance the generalization ability of the model to novel macromolecules. First, FSCC uses contrastive learning to pre-train the model on a sufficient number of labeled macromolecules. Second, FSCC uses distribution calibration to re-train the classifier, enabling the model to classify macromolecules of novel classes (unseen class in the pre-training). Distribution calibration transfers learned knowledge in the pre-training stage to novel macromolecules with limited labeled macromolecules of novel class. Experiments were performed on both synthetic and real datasets. On the synthetic datasets, compared with the state-of-the-art (SOTA) method based on supervised deep learning, FSCC achieves competitive performance. To achieve such performance, FSCC only needs five labeled macromolecules per novel class. However, the SOTA method needs 1100 ∼ 1500 labeled macromolecules per novel class. On the real datasets, FSCC improves the accuracy by 5% ∼ 16% when compared to the baseline model. These demonstrate good generalization ability of contrastive learning and calibration distribution to classify novel macromolecules with ...
Keywords	few-shot learning ; cryo-ET ; macromolecule classification ; contrastive learning ; distribution calibration ; Biology (General) ; QH301-705.5
Subject code	006
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Novel Three-Gene Model Predicts Prognosis and Therapeutic Sensitivity in Esophageal Squamous Cell Carcinoma

Fa-Min Zeng / Jian-Zhong He / Shao-Hong Wang / De-kai Liu / Xiu-E. Xu / Jian-Yi Wu / En-Min Li / Li-Yan Xu

BioMed Research International, Vol

2019 Volume 2019

Abstract	To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have superiority over the use of single biomarkers. Our previous studies have identified the crucial role of ezrin in ESCC progression, which prompted us to hypothesize that ezrin-associated proteins contribute to the pathobiology of ESCC. Herein, we explored the clinical value of a molecular model constructed based on ezrin-associated proteins in ESCC patients. We revealed that the ezrin-associated proteins (MYC, PDIA3, and ITGA5B1) correlated with the overall survival (OS) and disease-free survival (DFS) of patients with ESCC. High expression of MYC was associated with advanced pTNM-stage (P=0.011), and PDIA3 and ITGA5B1 were correlated with both lymph node metastasis (PDIA3: P<0.001; ITGA5B1: P=0.001) and pTNM-stage (PDIA3: P=0.001; ITGA5B1: P=0.009). Furthermore, we found that, compared with the current TNM staging system, the molecular model elicited from the expression of MYC, PDIA3, and ITGA5B1 shows higher accuracy in predicting OS (P<0.001) or DFS (P<0.001) in ESCC patients. Moreover, ROC and regression analysis demonstrated that this model was an independent predictor for OS and DFS, which could also help determine a subgroup of ESCC patients that may benefit from chemoradiotherapy. In conclusion, our study has identified a novel molecular prognosis model, which may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for ESCC treatment.
Keywords	Medicine ; R
Subject code	616
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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