HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma

Yuan, Xin; Liu, Kun; Li, Y; Zhang, A Z; Wang, X L; Chen, Jiang; Liang, Wei; Zhang, H J; Pang, Li; Li, M; Yang, Lan; Yan, Qi; Zheng, Qi; Li, F; Hu, Jian

doi:10.1007/s12094-021-02642-5

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…In ESCC animal studies, the inhibition of CCL2-CCR2 axis could suppress tumor growth by blocking M2 macrophage recruitment and thus enhance the antitumor effect of CD8 + T cells [ 29 ]. A study showed that HPV16 could accelerate cell migration and invasion of ESCC by recruiting tumor-associated macrophages [ 30 ]. These findings suggest that the tumor microenvironment plays a key role in tumor development.…”

Section: Discussionmentioning

confidence: 99%

Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data

Deng

Huang

et al. 2023

CCHTS

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Background: Bridging integrator 3 (BIN3) has been reported to play a key role in certain tumors. Nevertheless, little is known about the role and clinical value of BIN3 in esophagus carcinoma (ESCA). This study aimed to investigate the pathological and prognostic role of BIN3 in ESCA patients. Methods: Genes significantly correlated with the prognosis of ESCA patients were screened and identified by comprehensive analysis of differentially expressed genes associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA. The expression of BIN3, pathological features correlation and subgroup overall survival analysis were performed using The Cancer Genome Atlas (TCGA) and GTEx databases. Moreover, the potential signaling pathways in which BIN3 was involved were analyzed by GO-KEGG enrichment analysis and gene set enrichment analysis (GSEA). Immune infiltrates correlation of BIN3 in ESCA was performed by TIMER and ssGSEA. The influence of BIN3 on epithelial-mesenchymal transition (EMT) was validated by western blot. Results: There were two differentially expressed genes related to the prognosis of ESCA patients, which were identified from three gene clusters associated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ESCA patients. The BIN3 mRNA level was found to be significantly decreased in ESCA compared to normal tissues (p < 0.05). The decreased expression of BIN3 in ESCA was significantly correlated with the clinical stage (p = 0.015), T stage (p < 0.05), histological type (p < 0.001), age (p < 0.05) and gender (p < 0.05). ESCA patients with high BIN3 expression were observed to be correlated with T stage (T3 & T4), age (＜＝60), gender (male), primary therapy outcome (PD) and columnar metaplasia (No) of favorable OS. GO-KEGG enrichment analysis revealed that BIN3 was involved in endocytosis. GSEA showed that several pathways were enriched in BIN3, such as O linked glycosylation of mucins, PID HNF3B pathway, biocarta TFF pathway, WP pregnane X receptor pathway, reactome regulation of beta cell development, WP Urea cycle and associated pathways and others. BIN3 was significantly related to the infiltration level of T cells (p < 0.001), Tregs (p < 0.001), B cells (p < 0.001), NK cells (p < 0.001), and macrophage M2 (p < 0.001). In addition, BIN3 overexpression inhibited N-cadherin expression and promoted E-cadherin expression in ESCA cell lines TE-1. Conclusion: These results suggest that BIN3 might be a potential prognostic biomarker in ESCA. BIN3 functions as a tumor-suppressor role in ESCA, which is significantly associated with the immune infiltration of ESCA.

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Section: Discussionmentioning

confidence: 99%

Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data

Deng

Huang

et al. 2023

CCHTS

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“…M0 macrophages differentiate into M1 and M2 macrophages under specific circumstances, which may play a role in the immune imbalance related to RA pathogenesis. A study of esophageal cancer showed that MMP-9 might regulate tumour-associated macrophages ( Yuan et al, 2021 ). Previous studies have shown that MMP-9 and macrophages participate in the pathogenesis of RA ( Xu et al, 2021 ) and OA ( Ostojic et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and analysis of a lncRNA–miRNA–mRNA competing endogenous RNA network from inflamed and normal synovial tissues after anterior cruciate ligament and/or meniscus injuries

Xiao

Yang²,

Ren³

et al. 2022

Front. Genet.

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Background: Despite ample evidence demonstrating that anterior cruciate ligament (ACL) and meniscus tears are associated with posttraumatic osteoarthritis (PTOA) development, the contributing factors remain unknown. Synovial inflammation has recently been recognized as a pivotal factor in the pathogenesis of OA. However, there is a lack of data on synovial profiles after ACL or meniscus injuries, which may contribute to PTOA.Methods: Twelve patients with ACL tears and/or meniscus injuries were recruited. During surgery, synovial tissues were obtained from the injured knees. The inflammation status of the synovium was characterized according to macroscopic criteria and histological synovitis grades. Then the synovial tissues were classified as control group or inflamed group. High-throughput RNA sequencing of the synovial samples (3 vs. 3) was conducted to identify differentially expressed (DE) RNAs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction (PPI) analyses were performed to investigate DE mRNAs. Next, competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses. Associations of the identified DE genes (DEGs) with infiltrating immune cells were explored using Pearson correlation analysis.Results: The results showed that 2793 mRNAs, 3392 lncRNAs and 211 miRNAs were significantly DE between two groups. The top 3 significantly upregulated GO terms and KEGG pathways were immune response, adaptive immune response and immune system process, systemic lupus erythematosus, haematopoietic cell lineage and cytokine–cytokine receptor interaction, respectively. In PPI networks, the top 10 hub genes were IL6, CCR7, C3, CCR5, CXCR3, CXCL8, IL2, CCR3, CCR2 and CXCL1. Seven mRNAs (EPHA5, GSN, ORC1, TLN2, SOX6, NKD2 and ADAMTS19), 4 lncRNAs (MIR4435-2HG, TNXA, CEROX1 and TMEM92-AS1) and 3 miRNAs (miR-486-5p, miR-199a-3p and miR-21-3p) were validated by quantitative real-time polymerase chain reaction and sub-networks were constructed. In correlation analysis, MMP9 correlated positively with M0 macrophages and plasma cells, NKD2 positively with CD8 T cells, and CCR7 and IL2RB positively with naive B cells.Conclusion: Our study provides foundational synovial inflammation profiles following knee trauma. The ceRNA and PPI networks provide new insight into the biological processes and underlying mechanisms of PTOA. The differential infiltration profiles of immune cells in synovium may contribute to PTOA development. This study also highlights immune-related DEGs as potential PTOA treatment biomarkers.

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“…Mast cells may contribute to an immunosuppressive environment that enables the persistence of HPV E7 protein induced pre-cancerous lesions ( Bergot et al, 2014 ). In an esophageal squamous cell carcinoma model, HPV16 infection promoted an M2 macrophage phenotype, thus, enhanced the invasion and metastasis ( Yuan et al, 2021a ). Tumor-associated neutrophils (TAN) can promote the formation of the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

A New HPV score System Predicts the Survival of Patients With Cervical Cancers

et al. 2021

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Persistent high-risk human papillomavirus (hrHPV) infection is confirmed as the major cause of cervical cancer. According to the HPV infection status, cervical cancer could be generalized as following three subgroups: HPV-negative, pure HPV-infection, and HPV-integration. Currently, the impact of HPV status on cervical cancer prognosis remains under dispute. Therefore, we explored the potential correlation between HPV status and the clinical outcome of cervical cancer, by establishing a robust prognostic predicting model based on a cervical cancer cohort using The Cancer Genome Atlas (TCGA) database. We performed an iCluster algorithm incorporating DNA copy number variation, SNP, DNA methylation, mRNA expression, and miRNA expression profile together and classified the cohort into three clusters. According to defined clusters, we established an HPV score system by weighing resultant gene alterations through random forest and COX models. This prediction tool could help to identify cervical cancer prognosis through evaluating individual HPV infection status and subsequent genetic modification, which might provide insights into HPV-related gene driven cervical cancer treatment strategies, yet its predictive power and robustness need to be further verified with independent cohorts.

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HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma

Cited by 6 publications

References 41 publications

Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data

Bridging Integrator 3 (BIN3) Downregulation Predicts a Poor Prognosis in Patients with Esophagus Carcinoma: A Study based on TCGA Data

Construction and analysis of a lncRNA–miRNA–mRNA competing endogenous RNA network from inflamed and normal synovial tissues after anterior cruciate ligament and/or meniscus injuries

A New HPV score System Predicts the Survival of Patients With Cervical Cancers

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