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The role of visfatin in cancer proliferation, angiogenesis, metastasis, drug resistance and clinical prognosis.

ABSTRACT: Visfatin, also known as nicotinamide phosphoribosyltransferase or pre-B-cell colony-enhancing factor (PBEF), is an adipocytokine secreted by adipocytes, macrophages and inflamed endothelial tissue. Related reports have indicated a positive correlation between the visfatin level and obesity and cancer risk. In addition to its original function, visfatin is multifunctional and plays critical roles in the promotion of several processes relevant to cancer progression including cancer cell proliferation, angiogenesis, metastasis and drug resistance. The relative expression of visfatin and the potential visfatin receptor on a pan-cancer scale was determined based on the transcriptome analysis data in The Cancer Genome Atlas. We further show the clinical association of its signaling axis with the survival of cancer patients, which reveals its prognostic power for specific cancer types. This review illustrates visfatin's biological functions related to cancer progression and demonstrates its clinical significance in predicting outcomes of cancer patients.

SUBMITTER: Lin TC

PROVIDER: S-EPMC6497876 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The role of visfatin in cancer proliferation, angiogenesis, metastasis, drug resistance and clinical prognosis.

Lin Tsung-Chieh TC

Cancer management and research 20190423

Visfatin, also known as nicotinamide phosphoribosyltransferase or pre-B-cell colony-enhancing factor (<i>PBEF</i>), is an adipocytokine secreted by adipocytes, macrophages and inflamed endothelial tissue. Related reports have indicated a positive correlation between the visfatin level and obesity and cancer risk. In addition to its original function, visfatin is multifunctional and plays critical roles in the promotion of several processes relevant to cancer progression including cancer cell pro ...[more]

PMID: 31114381

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Project description:Purpose:Ovarian cancer is a major type of gynecological malignancy which characterized by the chemoresistance, heterogeneity and highly metastasis. However, the mechanism underlying the progression of ovarian cancer remains elusive. Pyruvate dehydrogenase kinase family plays critical roles in tumorigenesis, and PDK4 has been demonstrated to be an oncogene in many types of cancers. The aim of this study was to identify the role of PDK4 in ovarian cancer. Methods:We explored the PDK4 expression according to the public database containing patients with different effect of chemotherapy. Cell proliferation and invasion assays were used to determine the function of PDK4. Mice xenograft experiment was conducted to test the pro-tumorigenesis function of PDK4 in vivo. Cell apoptosis under treatment of chemo drugs was detected by flow cytometry and TUNEL analysis. Spheroid formation assay and CD133+ cell population were used to determine the PDK4-induced stem-like traits. Immunohistochemical staining was performed to test the expression of PDK4 in ovarian cancer tissues, and Kaplan- Meier curve with log-rank test was performed to determine the association between PDK4 expression and ovarian cancer patients' prognosis. Results:Overexpression of PDK4 markedly promoted cell proliferation, invasion and tumor growth in vivo. Furthermore, PDK4 confers cell resistant to chemotherapy-induced apoptosis. Mechanically, we demonstrated that PDK4 induced stem-like traits. Meanwhile, PDK4 expression was significantly evaluated in ovarian cancer tissues compared to that in adjacent non-cancer tissues, and high expression of PDK4 was associated with poor overall survival and progression-free survival of ovarian cancer patients. Conclusion:These results identify a novel role of PDK4 in regulating cell stem-like trait, which directly enhances the cell proliferation, invasion and chemoresistance in ovarian cancer, and targeting PDK4 could be a potential approach for ovarian cancer treatments.

Project description:BackgroundAngiogenesis and remodeling (AR) is necessary for the growth and metastasis of cancers. Although AR related genes involved in this process are reported, the correlation between AR and clinical outcome, immune cell infiltration, and immunotherapy is still unknown in diverse cancers. This study aimed to investigate the role of AR in the tumor immune microenvironment (TIME) in pan-cancer, and explore its values in prognostic prediction and therapeutic responses.MethodsFirstly, AR genes (including angiogenesis genes and blood vessel remodeling genes) are collected from MsigDB database. The differential expression, and prognostic value of AR genes were studied in 33 tumor types based on TCGA and GTEx data. The AR score of each sample was calculated using the "ssGSEA" function of R package "GSVA" in pan-cancer. The correlation of the AR score with TIME index, such as the amount of stromal and immune components and the immune cell infiltration, was evaluated via integrating multiple computational methods. And we also utilized IMvigor210 and GSE78220 data to explore the prediction value of the AR score on the immunotherapy response.ResultsSignificant differences in AR gene expression between tumors and adjacent normal tissues were found in most cancer types. The AR score varied depending on the types of tumors, and high score was related to worse survival in various tumors, such as pancreatic and stomach adenocarcinoma and so on. Moreover, the AR score was further explored to be positively correlated with proportions and pathways of immune and stromal in TIME. And the AR score was positively correlated with immunosuppressive cells, including TAMs and iTregs, while negatively with CD8+ T cells. Further analysis revealed that patients with high AR had worse therapy efficacy and survival status in bladder cancer and melanomas.ConclusionsOur systematic analysis revealed that AR is closely associated TIME, and prognosis, and clinical characteristics in multiple cancers. Targeting AR genes may activate immune microenvironment and increase the efficacy of immunotherapy.

Dataset Information

The role of visfatin in cancer proliferation, angiogenesis, metastasis, drug resistance and clinical prognosis.

Publications

The role of visfatin in cancer proliferation, angiogenesis, metastasis, drug resistance and clinical prognosis.

Similar Datasets

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