S100A7 as a potential diagnostic and prognostic biomarker of esophageal squamous cell carcinoma promotes M2 macrophage infiltration and angiogenesis

Lu, Zhiliang; Zheng, Sufei; Liu, Chengming; Wang, Xinfeng; Zhang, Guochao; Wang, Feng; Wang, Sihui; Huang, Jianbing; Mao, Shuangshuang; Lei, Yuanyuan; Wang, Zhanyu; Sun, Nan; He, Jie

doi:10.1002/ctm2.459

Cited by 38 publications

(35 citation statements)

References 41 publications

(83 reference statements)

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“…It has been shown that activation of S100A7-regulated pathways is linked to increased cancer-associated angiogenesis [ 30 ], the promotion of M2 macrophage infiltration in the tumor microenvironment [ 31 ] and enhancement of tumorsphere growth [ 1 ]. Furthermore, the upregulated excretion of S100A7 protein in serum and urine was reported in individuals with cancers such as esophageal squamous cell carcinoma [ 31 ], cutaneous melanoma [ 32 ] and bladder squamous cell carcinoma [ 33 ], suggesting S100A7 might be a potential diagnostic and prognostic biomarker in cancers. These observations corroborate our current results, showing that S100A7 was highly expressed in most investigated tumors, and that a high S100A7 expression was associated with poor prognosis in most tumors.…”

Section: Discussionmentioning

confidence: 99%

A Pancancer Analysis of the Oncogenic Role of S100 Calcium Binding Protein A7 (S100A7) in Human Tumors

Peng

Tsukamoto

Okumura

et al. 2022

Biology

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Background: Although emerging studies support the relationship between S100 calcium binding protein A7 (S100A7) and various cancers, no pancancer analysis of S100A7 is available thus far. Methods: We investigated the potential oncogenic roles of S100A7 across 33 tumors based on datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Moreover, a survival prognosis analysis was performed with the gene expression profiling interactive analysis (GEPIA) web server and Kaplan–Meier plotter, followed by the genetic alteration analysis of S100A7 and enrichment analysis of S100A7-related genes. Results: S100A7 was highly expressed in most types of cancers, and remarkable associations were found between S100A7 expression and the prognosis of cancer patients. S100A7 expression was associated with the expression of DNA methyltransferase and mismatch repair genes in head and neck squamous cell carcinoma, the infiltration of CD8+ T cells and cancer-associated fibroblasts in different tumors. Moreover, glycosaminoglycan degradation and lysosome-associated functions were involved in the functional mechanisms of S100A7. Conclusions: The current pancancer study shows a relatively integrative understanding of the carcinogenic involvement of S100A7 in numerous types of cancers.

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Section: Discussionmentioning

confidence: 99%

A Pancancer Analysis of the Oncogenic Role of S100 Calcium Binding Protein A7 (S100A7) in Human Tumors

Peng

Tsukamoto

Okumura

et al. 2022

Biology

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“…Considering that the interaction between S100 Ca 2+ -binding proteins and RAGE promotes tumor progression also stimulating invasive effects [ 44 , 66 – 69 ], we next aimed to explore whether S100A8/A9-RAGE activation prompts the migration of TNBC cells. S100A8/A9 treatment stimulated migratory effects in TNBC cells overexpressing RAGE, however these responses were reduced targeting either RAGE or FAK and by knocking-down the expression of the YAP/TEAD target FLNA (Fig.…”

Section: Resultsmentioning

confidence: 99%

Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC)

Rigiracciolo

Nohata

Lappano

et al. 2022

J Exp Clin Cancer Res

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Background Understanding the intricate signaling network involved in triple-negative breast cancer (TNBC) represents a challenge for developing novel therapeutic approaches. Here, we aim to provide novel mechanistic insights on the function of the S100A8/A9-RAGE system in TNBC. Methods TNM plot analyzer, Kaplan-Meier plotter, Meta-analysis, GEPIA2 and GOBO publicly available datasets were used to evaluate the clinical significance of S100A8/A9 and expression levels of S100A8/A9, RAGE and Filamin family members in breast cancer (BC) subtypes. METABRIC database and Cox proportional hazard model defined the clinical impact of high RAGE expression in BC patients. Multiple bioinformatics programs identified the main enriched pathways within high RAGE expression BC cohorts. By lentiviral system, TNBC cells were engineered to overexpress RAGE. Western blotting, immunofluorescence, nucleus/cytoplasm fractionation, qRT-PCR, gene silencing and luciferase experiments were performed to identify signal transduction mediators engaged by RAGE upon stimulation with S100A8/A9 in TNBC cells. Proliferation, colony formation and transwell migration assays were carried out to evaluate the growth and migratory capacity of TNBC cells. Statistical analysis was performed by ANOVA and independent t-tests. Results We found a remarkable high expression of S100A8 and S100A9 in BC, particularly in HER2-positive and TNBC, with the latter associated to worst clinical outcomes. In addition, high RAGE expression correlated with a poor overall survival in BC. Next, we determined that the S100A8/A9-RAGE system triggers FAK activation by engaging a cytoskeleton mechanosensing complex in TNBC cells. Through bioinformatics analysis, we identified the Hippo pathway as the most enriched in BC patients expressing high RAGE levels. In accordance with these data, we demonstrated the involvement of S100A8/A9-RAGE-FAK signaling in the control of Hippo/YAP activities, and we established the crucial contribution of RAGE-FAK-YAP circuitry in the growth and migratory effects initiated by S100A8/A9 in TNBC cells. Conclusions The present study provides novel mechanistic insights on RAGE actions in TNBC. Moreover, our findings suggest that RAGE-FAK-YAP transduction pathway could be exploited as a druggable system halting the aggressive TNBC subtype.

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“…It had been reported that LOR and FLG were abnormally upregulated in atopic dermatitis, which played a critical role in disease development [ 24 ]. It has been well known that OLP is a hyperkeratotic mucosal disease, and recently, researchers have found that the expression of filaggrin and filaggrin-2 markedly increased in OLP patients [ 25 ], which might suggest that filaggrin is essential to keratinization. Our findings about FLG also provide strong evidence for this viewpoint.…”

Section: Discussionmentioning

confidence: 99%

“…S100A7, s100 calcium binding protein A7, is a member of S100 protein family. Researchers have found that it was abnormally upregulated in esophageal squamous cell carcinoma (ESCC), which might promote tumor progression by impacting M2 macrophage infiltration and angiogenesis; thereby, S100A7 was expected to act as a therapeutic target for ESCC treatment [ 25 ]. Moreover, based on whole gene expression profiling, it had been identified as a novel candidate biomarker related to OSCC [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Key Biomarkers and Immune Infiltration in Oral Lichen Planus

et al. 2022

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Background. Oral lichen planus (OLP) is a chronic autoimmune oral mucosal disease that seriously affects the life quality of the patients. But till now, the exact etiology and pathogenesis of OLP remain unclear. Our study is aimed at finding the key molecules and pathways involved in the pathogenesis mechanisms of OLP, providing more effective therapeutic strategies for OLP. Methods. Data from GSE52130 were downloaded from GEO datasets for analysis. Then, we carried out enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology (GO) and KEGG pathway analyses. Next, the CIBERSORT algorithm was used to assess immune cell infiltration in OLP patients. Furthermore, we also constructed a protein-protein interaction network using STRING and Cytoscape and simultaneously sought potential transcription factors plug-in including MCODE CytoHubba and iRegulon. In addition, ROC analysis was employed to assess the diagnostic performance of these hub genes. Lastly, we identified 6 promising novel drugs to treat OLP through Connectivity Map. Results. We illustrated that 255 DEGs were mainly enriched in the focal adhesion pathway and metabolism pathways. Besides, Cibersort analysis showed that M1 macrophages, T follicular helper cells, and T regulatory cells are more infiltrated in OLP samples. In addition, ROC analysis demonstrated that these hub genes owned higher diagnostic value in OLP, in which SPRR1B had the highest diagnostic value. And we also predicted that SOX7 was the most relevant transcription factor of those hub genes. Lastly, through the CMap database, we identified 6 small molecules as possible treatment drugs of OLP. Conclusion. Our research identified that SPRR1B could be used as potential biomarkers for the early diagnosis of OLP. In addition, as a chronic autoimmune oral mucosal disease, OLP has different infiltration types of immune cells. Furthermore, 6 small molecules were proposed as promising novel treatment drugs for OLP patients. Therefore, our research may provide new impetus for the development of effective OLP biological treatment options.

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S100A7 as a potential diagnostic and prognostic biomarker of esophageal squamous cell carcinoma promotes M2 macrophage infiltration and angiogenesis

Cited by 38 publications

References 41 publications

A Pancancer Analysis of the Oncogenic Role of S100 Calcium Binding Protein A7 (S100A7) in Human Tumors

A Pancancer Analysis of the Oncogenic Role of S100 Calcium Binding Protein A7 (S100A7) in Human Tumors

Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC)

Identification of Potential Key Biomarkers and Immune Infiltration in Oral Lichen Planus

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