Expression and significance of insulin-like growth factor binding protein-related protein 1 in pancreatic neoplasms and its relationship with tumor microenvironment

Abstract

Objective To observe the expression of insulin-like growth factor binding protein-related protein 1(IGFBPrP1) in human pancreatic tumor tissues and investigate its significance and relationship with clinic pathological characteristics and tumor microenvironment of the pancreatic neoplasms. Methods A total of 236 patients with surgically resected pancreatic tissue from January 2007 to December 2017 were selected from the First Hospital of Shanxi Medical University. Totally 236 patients were divided into paracancer control group (normal pancreatic tissue adjacent to the tumor, n=111), benign group (benign or low-grade malignant tumor such as solid pseudopapillary tumor, n=37), and malignant group (malignant tumors such as pancreatic ductal adenocarcinoma, n=88). The histomorphology and collagen deposition were observed using hematoxylin-eosin (H-E) staining and Sirius red staining in the three groups. The expressions of IGFBPrP1, transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA)and collagen type Ⅰ of pancreatic tissues in the three groups were detected by immunohistochemical staining. The relationship between IGFBPrP1 and TGFβ1, α-SMA or collagen type Ⅰ, and the relathionship between IGFBPrP1 and clinicopathological features of the pancreatic neoplasms were analyzed. T test and one-way analysis of variance were used for statistical analysis, and Spearman rank correlation test was used for correlation analysis. Results In benign group and malignant group, there were obvious cell atypia, and the cell atypia of malignant group was more significant than benign group. The contents of collagen fibers in benign group and malignant group were significantly higher than that in paracancer control group. IGFBPrP1, TGFβ1, α-SMA and collagen typeⅠwere highly expressed in the endochylema of the tumor cells and (or) the myofibroblast. The expression level of IGFBPrP1 in highly differentiated ductal adenocarcinoma was significantly higher than that in moderately and poorly differentiated ductal adenocarcinoma ((9.46±2.10)×104 vs. (6.48±1.38)×104 and (6.07±1.29)×104); t=7.430 and 6.767, both P<0.05). The expression of IGFBPrP1 in human pancreatic neoplasms was positively correlated with TGFβ1, α-SMA and collagen typeⅠ(r=0.530, 0.619, 0.625; all P<0.05). Conclusions IGFBPrP1 is highly expressed in pancreatic tumor tissue and its expression level may correlate with the histological grade of pancreatic neoplasms. The expression of IGFBPrP1 in human pancreatic tumor tissues may be accompanied by the activation of pancreatic stellate cells and the generation of cancer-related fibroblasts, and IGFBPrP1 may involve in the formation of tumor by changing the tumor microenvironment. Key words: Insulin-like growth factor binding protein-related protein 1; Pancreatic neoplasms; Tumor microenvironment; Transforming growth factor beta1; α-smooth muscle actin; Collagen type Ⅰ