Abstract
It has been reported that serum insulin-like growth factor-binding protein 2 (IGFBP2) levels are elevated in various types of cancers. However, the clinicopathologic and prognostic implications of circulating IGFBP2 have never been investigated in gastric cancer. We tested IGFBP2 levels in the sera of 118 gastric cancer patients and 34 healthy controls using enzyme-linked immunosorbent assay (ELISA). The mean serum IGFBP2 level was significantly elevated in the gastric cancer patients compared to controls (805.23 ± 590.56 ng/ml vs. 459.61 ± 277.01 ng/ml; P < 0.001). Serum IGFBP2 levels were significantly higher in larger (> 6 cm) tumors (956.8 ± 734.0 ng/ml vs. 548.6 ± 364.0 ng/ml; P = 0.007) and in higher (T3/4) T stages (854.8 ± 621.4 ng/ml vs. 546.5 ± 315.1 ng/ml; P = 0.037). Multivariate Cox analysis showed that higher serum IGFBP2 level (> 400.01 ng/ml) was an independent prognostic factor predicting worse overall survival in patients with gastric cancer (hazard ratio (HR): 3.749, P = 0.034). When we divided patients into four groups based on blood IGFBP2 levels, survival was stratified. The HRs for death in the 3rd and 4th quartiles of serum IGFBP2 levels in comparison to that in the 1st quartile were 2.527 (P = 0.043) and 3.092 (P = 0.012). In conclusion, circulating IGFBP2 has potential as a biomarker predicting prognosis for gastric cancer patients.
Highlights
Insulin-like growth factors (IGFs) are regulatory peptides with a number of biological functions, such as cell proliferation, differentiation, and anti-apoptosis [1, 2]
It has been reported that serum insulin-like growth factor-binding protein 2 (IGFBP2) levels are elevated in various types of cancers
Serum IGFBP2 levels were correlated with tumor size in lung cancer [18], and the levels significantly dropped after curative resection in patients with colorectal cancer [17]; both observations implicate serum IGFBP2 as an indicator for tumor burden
Summary
Insulin-like growth factors (IGFs) are regulatory peptides with a number of biological functions, such as cell proliferation, differentiation, and anti-apoptosis [1, 2]. The action of IGFs are modulated by the IGFBPs in a positive or negative way, depending on tissue type and physiologic status [4]. Previous reports demonstrated increased expression of IGFBP2 in various types of cancer tissue, including glioma [11], colorectal cancer [12], lung cancer [13], and gastric cancer [14, 15], and high expression of IGFBP2 was associated with worse survival. Since IGFBP2 is a secretory protein, it has been observed that serum IGFBP2 was elevated in cancer patients compared to healthy individuals for ovarian cancer [16], colorectal cancer [17], and lung cancer [18]. High circulating IGFBP2 level was considered a poor prognostic factor in these tumors. Serum IGFBP2 levels were correlated with tumor size in lung cancer [18], and the levels significantly dropped after curative resection in patients with colorectal cancer [17]; both observations implicate serum IGFBP2 as an indicator for tumor burden
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