Abstract
BackgroundPigment 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.MethodsWe 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.ResultsA 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).ConclusionsLow 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.
Highlights
Pigment epithelial-derived factor (PEDF) was first identified as a protein factor secreted by human retinal pigment epithelium cells [1]
We further investigated if Pigment epithelium derived factor (PEDF) protein expression is correlated with tumor size, lymph node invasion, and distal metastasis, each of which could contribute to tumor progression
This study shows that the decreased PEDF expression at protein level is associated with more adverse clinical outcomes in cancer patients, manifested by higher TNM staging, higher tumor grading, and a significantly shorter overall survival
Summary
Pigment epithelial-derived factor (PEDF) was first identified as a protein factor secreted by human retinal pigment epithelium cells [1] It is called serine protease inhibitor F1 (SERPINF1) and belongs to the serine protease inhibitor (serpin) superfamily. PLXDC1’s tumor blood vessel expression was found in a wide range of cancer types, including liver cancer, breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, lung cancer, neuroblastoma and sarcomas [13,14,15,16,17] This high specificity of PEDF receptor’s expression in tumor blood vessels matches the specificity of PEDF’s tumor inhibitory effect. 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. The differential clinical outcome among patients with various PEDF expression suggests its prognostic value
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