Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

Arroyo‐Solera, Irene; Pavón, Miguel Ángel; León, Xavier; López, Montserrat; Gallardo, Alberto; Céspedes, María Virtudes; Casanova, Isolda; Pallarès, Víctor; López‐Pousa, Antonio; Mangues, María Antònia; Barnadas, Agustí; Quer, Miquel; Mangues, Ramón

doi:10.1002/hed.25437

Cited by 26 publications

(16 citation statements)

References 41 publications

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“…The plasminogen activator inhibitor-1 (PAI-1) encoded by SERPINE1 was an important regulator of the uPA system, which was supposed to inhibit the activation of uPA, but paradoxical studies revealed that SERPINE1 might play a role in promoting the carcinogenesis of many cancers [23]. Many investigations have implied that SERPINE1 is overexpressed in various cancers, including GC [24], head and neck cancer [25] and colorectal cancer [26], and this overexpression correlated with the aggressiveness and invasiveness of tumor cells. Additionally, the downregulation of SERPINE1 suggested a suppressive effect on the phenotype of glioma tumor cells by activating the p53 signaling pathway and suppressing the adverse invasion and metastasis of nasopharyngeal carcinoma cells in vitro [27][28].…”

Section: Discussionmentioning

confidence: 99%

Identification of pivotal genes associated with the prognosis of gastric carcinoma through integrated analysis

et al. 2021

Bioscience Reports

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Purpose: Detecting and diagnosing gastric cancer (GC) during its early period remains greatly difficult. Our analysis was performed to detect core genes correlated with GC and explore their prognostic values. Methods: Microarray datasets from the GEO (GSE54129) and TCGA-stomach adenocarcinoma (STAD) datasets were applied for common differentially coexpressed genes using differential gene expression analysis and weighted gene coexpression network analysis (WGCNA). Functional enrichment analysis and protein-protein interaction (PPI) network analysis of differentially coexpressed genes were performed. We identified hub genes via the CytoHubba plugin. Prognostic values of hub genes were explored. Afterward, GSEA was used to analyze survival-related hub genes. Finally, the tumor-infiltrating immune cell (TIC) abundance profiles were estimated. Results: Sixty common differentially co-expressed genes were found. Functional enrichment analysis implied that cell−cell junction organization and cell adhesion molecules were primarily enriched. Hub genes were identified using the degree, edge percolated component (EPC), maximal clique centrality (MCC), and maximum neighborhood component (MNC) algorithms, and SERPINE1 was highly associated with the prognosis of GC patients. Moreover, GSEA demonstrated that ECM receptor interactions and pathways in cancers were correlated with SERPINE1 expression. CIBERSORT analysis of the proportion of TICs suggested that CD8+ T cell and T cell regulation were negatively associated with SERPINE1 expression, showing that SERPINE1 may inhibit the immune-dominant status of the tumor microenvironment in GC. Conclusions: Our analysis shows that SERPINE1 is closely correlated with the tumorigenesis and progression of GC. Furthermore, SERPINE1 acts as a candidate therapeutic target and prognostic biomarker of GC.

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Section: Discussionmentioning

confidence: 99%

Identification of pivotal genes associated with the prognosis of gastric carcinoma through integrated analysis

et al. 2021

Bioscience Reports

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“…Our study indicated that upregulated THBS1 was associated with poor prognosis in gastric cancer. SERPINE1 functions as the principal inhibitor of tPA and uPA, which promotes the metastasis of tumors [27,28]. Our study showed that upregulated SERPINE1 was associated with a poor prognosis in gastric cancer.…”

Section: Discussionmentioning

confidence: 75%

Expression Pattern and Prognostic Value of p53-Pathway in Gastric Cancer

Li¹,

Shi

2021

Preprint

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Background: Gastric cancer is one of the most common cancer across the world. Increasing evidence suggest that p53-pathway plays a critical role in the initiation, progress and therapy of gastric cancer. However, the prognostic value of p53-pathway in gastric cancer is not fully understood. Methods: A total of 67 p53-pathway-related genes and corresponding clinical information of 415 gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The consensus clustering algorithm were performed to analyze the expression level of all p53-pathway related genes. Based on the differentially expressed genes between different subgroups, Cox regression analysis were used to construct an independent prognostic signature, which was further validated in two external datasets. Results: 3 subgroups of patients with significant different survival outcome were identified according to the expression level of p53-pathway-related genes. Comparison of gene expression between those subgroups identified 12 differentially expressed genes, 3 (THBS1, SERPINE1 and GADD45B) of which were significantly associated with the overall survival outcome. We further constructed a 3-gene signature as independence prognosis signature with promising performance in survival prediction of gastric cancer. Conclusions: This study provides a potential prognostic signature for predicting prognosis of gastric cancer patients, which may benefit individual therapy of gastric cancer.

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“…SERPINE1 is considered an oncogene in various types of cancers and can enable cancer cells to gain new properties such as migration, EMT, and apoptosis resistance ( 25 – 26 ).The expression of SERPINE1 was quantified in four HNSCC cell lines ( Figure 7A ). Then, in order to measure the potential effects of SERPINE1 on LSCC, we transfected SERPINE1 siRNAs to knockdown its expression in Fadu cells.…”

Section: Resultsmentioning

confidence: 99%

Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1

Fan

et al. 2020

Front. Oncol.

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Laryngeal squamous cell carcinoma (LSCC) arises from the squamous epithelium of the larynx and is associated with a high incidence of cervical lymph node metastasis. MicroRNAs (miRNAs) play a crucial role in the epigenetic regulation of cellular biological processes, including cancer metastasis. However, the molecular mechanisms of specific miRNAs responsible for LSCC metastasis and their clinical significance have yet to be fully elucidated. In this study, LSCC cohort datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were downloaded and examined by comprehensive bioinformatics analysis, which revealed that upregulation of mRNA SERPINE1 and downregulation of miR-181c-5p were associated with unfavorable overall survival. Our analysis showed that SERPINE1 expression negatively correlated with the expression level of miR-181c-5p in our LSCC patient samples. Silencing of miR-181c-5p expression promoted cell migration and invasion in cell lines, whereas the overexpression of miR-181c-5p suppressed cell migration and epithelial-to-mesenchymal transition (EMT) through the downregulation of SERPINE1. Further analysis showed that the enhancement effect on EMT and metastasis induced by silencing miR-181c-5p could be rescued through knockdown of SERPINE1 expression in vitro. Collectively, our findings indicated that miR-181c-5p acted as an EMT suppressor miRNA by downregulation of SERPINE1 in LSCC and offers novel strategies for the prevention of metastasis in LSCC.

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Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

Cited by 26 publications

References 41 publications

Identification of pivotal genes associated with the prognosis of gastric carcinoma through integrated analysis

Identification of pivotal genes associated with the prognosis of gastric carcinoma through integrated analysis

Expression Pattern and Prognostic Value of p53-Pathway in Gastric Cancer

Down-Regulation of MiR-181c-5p Promotes Epithelial-to-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma via Targeting SERPINE1

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