Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
J Cell Physiol. 2019 Dec;234(12):23537-23546. doi: 10.1002/jcp.28922. Epub 2019 Jun 4.
Insulin-like growth factor binding protein-3 (IGFBP-3) and its newly discovered death receptor (IGFBP-3R) have been reported to involve in a wide variety of cancers. However, their role in pancreatic ductal adenocarcinoma (PDAC) has not been elucidated yet. Here, 478 pancreatic cancers were screened for primary PDAC tumors. The samples were evaluated using quantitative reverse-transcriptase polymerase chain reaction, western blotting, and immunohistochemistry staining. The results indicated that relative IGFBP-3 mRNA expression and its protein level were reduced stage dependently in the PDAC tumors (p < .001 and p < .05, respectively). The subcellular distribution of IGFBP-3 was mainly nuclear only in Stage 0 + 1 (about 150% compared to adjacent normal tissues [p < .05]). The value for IGFBP-3R messenger RNA (mRNA) and protein were also reduced in tumors in compared to adjacent normal pancreatic tissues (p < .05). The Kaplan-Meier analysis also showed that mRNA expression of IGFBP-3 and IGFBP-3R was positively associated with survival, (p = .001). In addition, there is a strong association between low expression of IGFBP-3 and tumor size (p = .032), the lymphatic invasion (p = .001), the TNM (tumor, node, metastasis) staging (p = .001), tumor differentiation (p = .001), and PNI status (p = .021). Down-regulation of IGFBP-3R was also correlated with the tumor size (p = .01), the lymphatic invasion (p = .012) TNM staging (p = .001), tumor differentiation (p = .021) and PNI status (p = .038). In conclusion, IGFBP-3 and its receptor were down-regulated and their expression was associated with poor prognosis of PDAC.
胰岛素样生长因子结合蛋白-3（IGFBP-3）及其新发现的死亡受体（IGFBP-3R）已被报道参与多种癌症。然而，它们在胰腺导管腺癌（PDAC）中的作用尚未阐明。在这里，对 478 例胰腺癌症进行了原发性 PDAC 肿瘤的筛查。使用定量逆转录聚合酶链反应、western blot 和免疫组织化学染色对样本进行评估。结果表明，PDAC 肿瘤中 IGFBP-3 的相对 mRNA 表达及其蛋白水平随疾病分期呈依赖性降低（p<0.001 和 p<0.05）。IGFBP-3 的亚细胞分布主要为核内，仅在 0+1 期（与相邻正常组织相比约为 150%[p<0.05]）。与相邻正常胰腺组织相比，肿瘤中 IGFBP-3R 信使 RNA（mRNA）和蛋白的水平也降低（p<0.05）。Kaplan-Meier 分析还表明，IGFBP-3 和 IGFBP-3R 的 mRNA 表达与生存呈正相关（p=0.001）。此外，IGFBP-3 低表达与肿瘤大小（p=0.032）、淋巴浸润（p=0.001）、TNM（肿瘤、淋巴结、转移）分期（p=0.001）、肿瘤分化（p=0.001）和 PNI 状态（p=0.021）之间存在强烈关联。IGFBP-3R 的下调也与肿瘤大小（p=0.01）、淋巴浸润（p=0.012）、TNM 分期（p=0.001）、肿瘤分化（p=0.021）和 PNI 状态（p=0.038）相关。总之，IGFBP-3 及其受体下调，其表达与 PDAC 的不良预后相关。
