Dataset Information

The up-regulation of Axl is associated with a poor prognosis and promotes proliferation in pancreatic ductal adenocarcinoma.

ABSTRACT: Pancreatic cancer is one of the most aggressive tumors and has a very poor prognosis. Recent studies show that Axl plays a key role in the occurrence and development of pancreatic cancer tumors. However, the expression and role of Axl in pancreatic cancer has not been reported. This study aimed to reveal the clinical significance of Axl expression in patients with pancreatic cancer and determine its mechanisms. In this study, western blot and immunohistochemistry were used to show that the expression of Axl in pancreatic cancer cell lines and tissues is significantly higher than its expression in corresponding non-tumor, normal tissues. By statistically analyzing clinical and pathological data, we found that there is a correlation between Axl expression and TNM stages and T stages, and Axl positive expression indicates a worse prognosis. According to in vitro assays, the proliferation of pancreatic cancer cells decreased, and the apoptosis level increased with Axl knockdown. Meanwhile, the knockdown of Axl increased the sensitivity of pancreatic cancer to gemcitabine. Moreover, AKT and ERK1/2 pathway proteins decreased with Axl knockdown. In conclusion, our results suggest that Axl is highly expressed in pancreatic cancer and is a prognostic factor. It may also be a potential biomarker and therapy target for pancreatic cancer.

SUBMITTER: Yu W

PROVIDER: S-EPMC6947122 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The up-regulation of Axl is associated with a poor prognosis and promotes proliferation in pancreatic ductal adenocarcinoma.

Yu Weihua W Ge Xiaolong X Lai Xusheng X Lv Jiemin J Wang Yong Y

International journal of clinical and experimental pathology 20190501 5

Pancreatic cancer is one of the most aggressive tumors and has a very poor prognosis. Recent studies show that Axl plays a key role in the occurrence and development of pancreatic cancer tumors. However, the expression and role of Axl in pancreatic cancer has not been reported. This study aimed to reveal the clinical significance of Axl expression in patients with pancreatic cancer and determine its mechanisms. In this study, western blot and immunohistochemistry were used to show that the expre ...[more]

PMID: 31933980

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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis. More effective biomarkers and treatment options remain to be discovered. Mitotic Spindle Positioning (MISP), also called C19orf21, has been reported to be upregulated in several malignancies. However, the effects of MISP on PDAC have yet to be investigated.Materials and methodsThe differential expression of MISP at the mRNA and protein levels were evaluated using Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases, and was further verified by quantitative real-time PCR and western blotting in PDAC cell lines. Correlations between MISP expression and clinical characteristics were explored using Kaplan-Meier Plotter Database and clinical data from The Cancer Genome Atlas (TCGA). CCK-8 assays, Transwell assays, and immunoblotting were used to determine the role of MISP in PDAC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were executed by the R package 'clusterProfiler'. Correlations between MISP expression and immune cell infiltration, immune checkpoints, immunophenoscore (IPS) and the tumor mutational burden (TMB) in PDAC were explored using the R package 'CIBERSORT', the Tumor Immune Estimation Resource 2.0 (TIMER2.0), and The Cancer Immunome Atlas (TCIA) database based on TCGA data.ResultMISP expression was significantly higher in pancreatic cancer tissues compared to normal pancreas tissues, which was associated with a poor prognosis. Increased expression of MISP was related to the proliferation, migration and invasion of PDAC cell lines. GO and KEGG pathway analyses determined that MISP is involved in the Ras signaling pathway and immune regulation. Higher expression of MISP was associated with decreased infiltration levels of activated CD4+ memory T cells, CD8+ T cells, M2 macrophages and neutrophils. Furthermore, increased MISP was associated with lower expression of immune checkpoint molecules, higher gene mutation burden and IPS.ConclusionsThis study reveals that MISP, which is associated with the progression and prognosis of PDAC, may exert a potential regulatory effect on immune infiltration and predict the response to immunotherapy in PDAC.

Dataset Information

The up-regulation of Axl is associated with a poor prognosis and promotes proliferation in pancreatic ductal adenocarcinoma.

Publications

The up-regulation of Axl is associated with a poor prognosis and promotes proliferation in pancreatic ductal adenocarcinoma.

Similar Datasets

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