The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance

Chen, Jinfeng; Ye, Lin; Zhang, Lijian; Jiang, Wen Guo

doi:10.3892/ijo_00000324

Cited by 8 publications

(1 citation statement)

References 24 publications

(34 reference statements)

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“…Reduced PEDF expression facilitates the progression of lung cancer due to the loss of PEDF-related suppression of tumor growth and motility. [ 60 ] PEDF is an adipocyte-secreted protein that acts as a pro-inflammatory factor by activating inflammatory signaling in several cell types. Therefore, PEDF contributes to the onset and maintenance of chronic inflammation in obesity and obesity-induced insulin resistance, and related complications such as MetSyn and type 2 diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

PEDF, a pleiotropic WTC-LI biomarker: Machine learning biomarker identification and validation

et al. 2021

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Biomarkers predict World Trade Center-Lung Injury (WTC-LI); however, there remains unaddressed multicollinearity in our serum cytokines, chemokines, and high-throughput platform datasets used to phenotype WTC-disease. To address this concern, we used automated, machine-learning, high-dimensional data pruning, and validated identified biomarkers. The parent cohort consisted of male, never-smoking firefighters with WTC-LI (FEV1, %Pred< lower limit of normal (LLN); n = 100) and controls (n = 127) and had their biomarkers assessed. Cases and controls (n = 15/group) underwent untargeted metabolomics, then feature selection performed on metabolites, cytokines, chemokines, and clinical data. Cytokines, chemokines, and clinical biomarkers were validated in the non-overlapping parent-cohort via binary logistic regression with 5-fold cross validation. Random forests of metabolites (n = 580), clinical biomarkers (n = 5), and previously assayed cytokines, chemokines (n = 106) identified that the top 5% of biomarkers important to class separation included pigment epithelium-derived factor (PEDF), macrophage derived chemokine (MDC), systolic blood pressure, macrophage inflammatory protein-4 (MIP-4), growth-regulated oncogene protein (GRO), monocyte chemoattractant protein-1 (MCP-1), apolipoprotein-AII (Apo-AII), cell membrane metabolites (sphingolipids, phospholipids), and branched-chain amino acids. Validated models via confounder-adjusted (age on 9/11, BMI, exposure, and pre-9/11 FEV1, %Pred) binary logistic regression had AUCROC [0.90(0.84–0.96)]. Decreased PEDF and MIP-4, and increased Apo-AII were associated with increased odds of WTC-LI. Increased GRO, MCP-1, and simultaneously decreased MDC were associated with decreased odds of WTC-LI. In conclusion, automated data pruning identified novel WTC-LI biomarkers; performance was validated in an independent cohort. One biomarker—PEDF, an antiangiogenic agent—is a novel, predictive biomarker of particulate-matter-related lung disease. Other biomarkers—GRO, MCP-1, MDC, MIP-4—reveal immune cell involvement in WTC-LI pathogenesis. Findings of our automated biomarker identification warrant further investigation into these potential pharmacotherapy targets.

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Section: Discussionmentioning

confidence: 99%

PEDF, a pleiotropic WTC-LI biomarker: Machine learning biomarker identification and validation

et al. 2021

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Association of pigment epithelium derived factor expression with cancer progression and prognosis: a meta-analysis study

Cheng

Song

2021

Discov Onc

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Background Pigment epithelium derived factor (PEDF) is a secreted protein that strongly suppresses angiogenesis and directly inhibits cancer cells proliferation. The differential expression of PEDF has been observed in multiple types of human tumors. However, it is unclear as to how PEDF expression is associated with cancer progression and if PEDF could serve as a prognostic marker for cancer patients. Methods We performed a comprehensive search for the studies on PEDF expression in 14 top-ranked types of solid tumor cancer with the highest incidence. A systemic approach was used to screen for qualified studies and to extract data. Meta-analysis was performed to investigate if PEDF expression is associated with the TNM staging, tumor size, lymph node invasion, distal metastasis and pathological grade of tumor in a pan-cancer manner. A Kaplan–Meier curve was plotted with the digitally-reconstituted patient survival data to study the effect of PEDF expression on the prognosis of cancer patients. Results A total of nine studies were selected, reviewed and analyzed. Meta-analysis suggested that decreased PEDF protein expression was associated with higher TNM staging (OR = 2.13, 95% CI: 1.61–2.81), larger tumor size (OR = 1.42, 95% CI: 1.1–1.84), larger possibility of lymph node invasion (OR = 1.68, 95% CI: 1.26–2.22) and higher pathological grade (OR = 1.6, 95% CI: 1.2–2.13). No correlation was found between PEDF expression and tumor distal metastasis, gender or age. In addition, low PEDF protein level in tumor tissue is correlated with shorter overall survival (P < 0.05). Conclusions Low PEDF protein expression in cancer is significantly associated with more advanced cancer progression and significantly poorer survival. The differential clinical outcome among patients with various PEDF expression suggests its prognostic value.

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Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

Yang

Liu

et al. 2016

Sci Rep

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Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer.

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The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance

Cited by 8 publications

References 24 publications

PEDF, a pleiotropic WTC-LI biomarker: Machine learning biomarker identification and validation

PEDF, a pleiotropic WTC-LI biomarker: Machine learning biomarker identification and validation

Association of pigment epithelium derived factor expression with cancer progression and prognosis: a meta-analysis study

Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

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