S100A8 as a Promising Biomarker and Oncogenic Immune Protein in the Tumor Microenvironment: An Integrative Pancancer Analysis

Wu, Zixuan; Jiang, Dongli; Huang, Xuyan; Cai, Minjie; Yuan, Kai; Huang, Peidong

doi:10.1155/2022/6947652

Cited by 8 publications

(14 citation statements)

References 43 publications

(42 reference statements)

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“…S100A8 could exhibit effects in inflammation, immune response, and cancer development, but its biological functions are complex. As previously reported, overexpression of S100A8 is associated with tumorigenesis and poor prognosis in various cancers ( 16 , 19 ). Wang H et al.…”

Section: Introductionsupporting

confidence: 70%

S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma

Lin,

Su,

Fang

et al. 2024

Front. Oncol.

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BackgroundS100A8, a calcium-binding protein belonging to the S100 family, is involved in immune responses and multiple tumor pathogens. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of B-cell lymphoma and remains incurable in 40% of patients. However, the role of S100A8 and its regulation of the immune response in DLBCL remain unclear.MethodsThe differential expression of S100A8 was identified via the GEO and TCGA databases. The prognostic role of S100A8 in DLBCL was calculated using the Kaplan-Meier curve. The function enrichment of differentially expressed genes (DEGs) was explored through GO, KEGG, GSEA, and PPI analysis. In our cohort, the expression of S100A8 was verified. Meanwhile, the biological function of S100A8 was applied after the inhibition of S100A8 in an in vitro experiment. The association between S100A8 and immune cell infiltration and treatment response in DLBCL was analyzed.ResultsS100A8 was significantly overexpressed and related to a poor prognosis in DLBCL patients. Function enrichment analysis revealed that DEGs were mainly enriched in the IL-17 signaling pathway. Our cohort also verified this point. In vitro experiments suggested that inhibition of S100A8 should promote cell apoptosis and suppress tumor growth. Single-cell RNA sequence analysis indicated that S100A8 might be associated with features of the tumor microenvironment (TME), and immune infiltration analyses discovered that S100A8 expression was involved in TME. In terms of drug screening, we predicted that many drugs were associated with preferable sensitivity.ConclusionElevated S100A8 expression is associated with a poor prognosis and immune infiltration in DLBCL. Inhibition of S100A8 could promote cell apoptosis and suppress tumor growth. Meanwhile, S100A8 has the potential to be a promising immunotherapeutic target for patients with DLBCL.

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Section: Introductionsupporting

confidence: 70%

S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma

Lin,

Su,

Fang

et al. 2024

Front. Oncol.

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“…A significant overexpression of MPO, PRTN3, S100A8 was found in 66.7% (n=8/12), 66.7% (n=8/12) and 83.3% (10/12) early stage GBC cases respectively. differentiation in melanoma and prostate cancers, although the biological function of S100A8 in cancer is not clear (32). Western blot analysis confirmed the overexpression of tissue MPO, PRTN3 and S100A8 in early stage GBC cases (Figure 8) and IHC analysis confirmed the overexpression of MPO in early stage GBC.…”

Section: Discussionmentioning

confidence: 82%

Quantitative tissue proteome profile reveals neutrophil degranulation and remodeling of extracellular matrix proteins in early stage gallbladder cancer

Akhtar

Jain²,

Kansal³

et al. 2023

Front. Oncol.

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Gallbladder cancer (GBC) is an aggressive malignancy of the gastrointestinal tract with a poor prognosis. It is important to understand the molecular processes associated with the pathogenesis of early stage GBC and identify proteins useful for diagnostic and therapeutic strategies. Here, we have carried out an iTRAQ-based quantitative proteomic analysis of tumor tissues from early stage GBC cases (stage I, n=7 and stage II, n=5) and non-tumor controls (n=6) from gallstone disease (GSD). We identified 357 differentially expressed proteins (DEPs) based on ≥ 2 unique peptides and ≥ 2 fold change with p value < 0.05. Pathway analysis using the STRING database showed, ‘neutrophil degranulation’ to be the major upregulated pathway that includes proteins such as MPO, PRTN3, S100A8, MMP9, DEFA1, AZU, and ‘ECM organization’ to be the major downregulated pathway that includes proteins such as COL14A1, COL1A2, COL6A1, COL6A2, COL6A3, BGN, DCN. Western blot and/or IHC analysis confirmed the elevated expression of MPO, PRTN3 and S100A8 in early stage of the disease. Based on the above results, we hypothesize that there is an increased neutrophil infiltration in tumor tissue and neutrophil degranulation leading to degradation of extracellular matrix (ECM) proteins promoting cancer cell invasion in the early stage GBC. Some of the proteins (MPO, MMP9, DEFA1) associated with ‘neutrophil degranulation’ showed the presence of ‘signal sequence’ suggesting their potential as circulatory markers for early detection of GBC. Overall, the study presents a protein dataset associated with early stage GBC.

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“…Concretely, immunosuppression‐related signature genes such as SPP1 and S100A8 were upregulated DEGs in metastasis groups. Secreted Phosphoprotein 1 (SPP1) was reported to be highly expressed in TAMs in tumor diseases 18,19 and related to less efficacy of anti‐PD‐L1 therapy, 20 S100A8 was reported to be associated with tumorigenesis and poor differentiation 21,22 . On the contrary, upregulation of immune activation associated genes like LAMP3, KLRB1, and APOA2 was also found in HCC without metastasis.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell profiling reveals the metastasis‐associated immune signature of hepatocellular carcinoma

Zhong,

Shi,

et al. 2024

Immunity Inflam & Disease

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AimMetastasis is the leading cause of mortality in hepatocellular carcinoma (HCC). The metastasis‐associated immune signature in HCC is worth exploring.MethodsBioinformatic analysis was conducted based on the single‐cell transcriptome data derived from HCC patients in different stages. Cellular composition, pseudotime state transition, and cell–cell interaction were further analyzed and verified.ResultsGenerally, HCC with metastasis exhibited suppressive immune microenvironment, while HCC without metastasis exhibited active immune microenvironment. Concretely, effector regulatory T cells (eTregs) were found to be enriched in HCC with metastasis. PHLDA1 was identified as one of exhaustion‐specific genes and verified to be associated with worse prognosis in HCC patients. Moreover, A novel cluster of CCR7+ dendritic cells (DCs) was identified with high expression of maturation and migration marker genes. Pseudotime analysis showed that inhibition of differentiation occurred in CCR7+ DCs rather than cDC1 in HCC with metastasis. Furthermore, interaction analysis showed that the reduction of CCR7+ DCs lead to impaired CCR7/CCL19 interaction in HCC with metastasis.ConclusionsHCC with metastasis exhibited upregulation of exhaustion‐specific genes of eTregs and inhibition of CCL signal of a novel DC cluster, which added new dimensions to the immune landscape and provided new immune therapeutic targets in advanced HCC.

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S100A8 as a Promising Biomarker and Oncogenic Immune Protein in the Tumor Microenvironment: An Integrative Pancancer Analysis

Cited by 8 publications

References 43 publications

S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma

S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma

Quantitative tissue proteome profile reveals neutrophil degranulation and remodeling of extracellular matrix proteins in early stage gallbladder cancer

Single‐cell profiling reveals the metastasis‐associated immune signature of hepatocellular carcinoma

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