Expressional and Prognostic Value of S100A16 in Pancreatic Cancer Via Integrated Bioinformatics Analyses

Tu, Gangping; Gao, Wenzhe; Liu, Ying; Dian, Yating; Xue, Bingyang; Niu, Lu; Yu, Xiao; Zhu, Hongwei

doi:10.3389/fcell.2021.645641

Cited by 14 publications

(14 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, COL11A1 was considered to be a prognostic marker of PDAC and was significantly related to tumor immune infiltration ( 51 ). Additionally, S100A16 was discovered as an important biomarker for the diagnosis and prognosis of PDAC ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic Characterization of the Clinical Relevance of KPNA4 in Pancreatic Ductal Adenocarcinoma

Bao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with poor prognosis. Karyopherin subunit alpha 4 (KPNA4) is a nuclear transport factor and plays tumor-promoting roles in multiple cancers. However, the roles of KPNA4 in PDAC still remain unknown. This study investigated the prognostic value of KPNA4 and its potential functions in PDAC and tumor microenvironment.MethodsLinkedOmics was utilized to screen genes with survival significance in PDAC. KPNA4 expression was analyzed using multiple datasets and verified in PDAC cells and clinical samples by qRT-PCR and immunohistochemistry. Clinical correlation and survival analyses were conducted to identify the clinical significance and prognostic value of KPNA4 in PDAC patients. Subsequently, KPNA4 was knocked down in PDAC cell lines, and CCK-8, colony formation and wound healing assays were performed to test the functions of KPNA4 in vitro. Immune infiltration analysis was performed to explore the potential roles of KPNA4 in the tumor microenvironment of PDAC. Moreover, functional analyses were conducted to explore the underlying mechanism of KPNA4 in the progression of PDAC.ResultsWe found KPNA4 was significantly upregulated in PDAC cells and tissues. KPNA4 expression was associated with tumor progression in PDAC patients. Survival analyses further revealed that KPNA4 could act as an independent predictor of unfavorable survival for PDAC patients. KPNA4 knockdown suppressed the viability, colony formation and migration of PDAC cells. Moreover, KPNA4 was correlated with immunosuppressive cells infiltration and T cell exhaustion in the tumor microenvironment of PDAC. Finally, functional analyses indicated the association of KPNA4 with focal adhesion kinase (FAK) signaling, and KPNA4 silencing significantly decreased the expression of FAK and PD-L1.ConclusionsThis study revealed that KPNA4 is an independent prognostic biomarker for PDAC and plays a tumor-promoting role by facilitating proliferation and migration of cancer cells and participating in immune infiltration, which may be mediated by FAK signaling and PD-L1 expression. These results provide a novel and potential therapeutic target for pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Systematic Characterization of the Clinical Relevance of KPNA4 in Pancreatic Ductal Adenocarcinoma

Bao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Among these genes, we identified S100A16 using multiple criteria, including its association with glioma, functional validation, and overall survival analysis. S100A16 is involved in various tumors, such as colorectal cancer, bladder cancer, pancreatic cancer, lung adenocarcinoma, cervical cancer, leukemia, and gastric cancer [37][38][39][40][41][42][43]. According to the CGGA database, S100A16 closely correlates with the survival rate of patients with primary gliomas.…”

Section: Discussionmentioning

confidence: 99%

An inhibitor of BRD4, GNE987, inhibits the growth of glioblastoma cells by targeting C-Myc and S100A16

Yang

et al. 2022

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Purpose Among children, glioblastomas (GBMs) are a relatively common type of brain tumor. BRD4 expression was elevated in GBM and negatively correlated with the prognosis of glioma. We investigated the anti-GBM effects of a novel BRD4 inhibitor GNE987. Methods We evaluated the anti-tumor effect of GNE987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, the size of xenografts, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In vitro experiments showed that GNE987 significantly degraded BRD4, inhibited the proliferation of GBM cells, blocked the cell cycle, and induced apoptosis. Similarly, in vivo experiments, GNE987 also inhibited GBM growth as seen from the size of xenografts and Ki67 immunohistochemical staining. Based on Western blotting, GNE987 can significantly reduce the protein level of C-Myc; meanwhile, we combined ChIP-seq with RNA-seq techniques to confirm that GNE987 downregulated the transcription of S100A16 by disturbing H3K27Ac. Furthermore, we validated that S100A16 is indispensable in GBM growth. Conclusion GNE987 may be effective against GBM that targets C-Myc expression and influences S100A16 transcription through downregulation of BRD4.

show abstract

“…S100A16 enhances the progression and metastasis of PAAD via FGF19 mediated AKT and ERK1/2 pathway (30). The study of Gangping Tu, et al showed that in comparison with the normal pancreas, S100A16 was highly expressed in tissues with PAAD, and the increase of its expression level may be correlated with an unfavorable prognosis of PAAD patients (35). CD40 is a cell surface member of the tumor necrosis factor (TNF) receptor superfamily.…”

Section: Discussionmentioning

confidence: 99%

An immune-related gene prognostic risk index for pancreatic adenocarcinoma

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

ObjectiveOur goal is to construct an immune-related gene prognostic risk index (IRGPRI) for pancreatic adenocarcinoma (PAAD), and to clarify the immune and molecular features in IRGPRI-defined PAAD subgroups and the benefit of immune checkpoint inhibitors (ICIs) therapy.MethodThrough differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and univariate Cox regression analysis, 16 immune-related hub genes were identified using the Cancer Genome Atlas (TCGA) PAAD dataset (n = 182) and immune gene set. From these genes, we constructed an IRGPRI with the Cox regression method and the IRGPRI was verified based on the Gene Expression Omnibus (GEO) dataset (n = 45). Then, we analyzed the immune and molecular features and the benefit of ICI therapy in IRGPRI-defined subgroups.ResultsFive genes, including S100A16, CD40, VCAM1, TNFRSF4 and TRAF1 were used to construct IRGPRI. As with the results of the GEO cohort, the overall survival (OS) was more favorable in low IRGPRI patients versus high IRGPRI patients. The composite results pointed out that low IRGPRI was associated with immune response-related pathways, high level of CTLA4, low KRAS and TP53 mutation rate, more infiltration of activated memory CD4+ T cells, CD8+ T cells, and more benefits from ICIs therapy. In comparison, high IRGPRI was associated with cancer-related pathways, low expression of CTLA4, high KRAS and TP53 mutation rate, more infiltration of M2 macrophages, and less benefit from ICIs therapies.ConclusionThis IRGPRI is an encouraging biomarker to define the prognosis, immune and molecular features, and benefits from ICIs treatments in PAAD.

show abstract

Expressional and Prognostic Value of S100A16 in Pancreatic Cancer Via Integrated Bioinformatics Analyses

Cited by 14 publications

References 38 publications

Systematic Characterization of the Clinical Relevance of KPNA4 in Pancreatic Ductal Adenocarcinoma

Systematic Characterization of the Clinical Relevance of KPNA4 in Pancreatic Ductal Adenocarcinoma

An inhibitor of BRD4, GNE987, inhibits the growth of glioblastoma cells by targeting C-Myc and S100A16

An immune-related gene prognostic risk index for pancreatic adenocarcinoma

Contact Info

Product

Resources

About