Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
Pathol Res Pract. 2020 May;216(5):152909. doi: 10.1016/j.prp.2020.152909. Epub 2020 Feb 29.
The insulin-like growth factor binding protein 6 (IGFBP6), as a specific inhibitor of IGF-Ⅱ, is a candidate human anti-oncogene in multiple tumors. However, the expression of IGFBP6 in colorectal cancer (CRC) and prognostic significance are unclear.
In this study, we examined colorectal cancer tissues and adjacent normal tissues to determine the expression levels of IGFBP6 mRNA and protein by quantitative reverse-transcription polymerase chain reaction and tissue microarray immunohistochemistry analysis respectively. Moreover, we explored the effects of IGFBP6 on cell growth, migration and invasion by Cell Counting Kit-8(CCK8), colony formation and transwell migration assays. We also investigated whether IGFBP6 expression in tumor tissue correlated with various clinical parameters, including overall survival by univariate and multivariate analyses RESULTS: Both IGFBP6 mRNA and protein levels were significantly lower in colorectal cancer tissues than in adjacent normal colon. Downregulating IGFBP6 using RNAi increased CRC cell proliferation, migration and invasion. Low IGFBP6 expression correlated with poor overall survival in both univariate and multivariate analyses.
Our data suggest that IGFBP6 may act as a tumor suppressor gene in the development of CRC, and that low IGFBP6 expression could be used as an independent prognostic biomarker in CRC.
胰岛素样生长因子结合蛋白 6（IGFBP6）作为 IGF-Ⅱ的特异性抑制剂，是多种肿瘤中潜在的人类抑癌基因。然而，IGFBP6 在结直肠癌（CRC）中的表达及其预后意义尚不清楚。
本研究通过定量逆转录聚合酶链反应（qRT-PCR）和组织微阵列免疫组织化学分析分别检测结直肠癌组织和相邻正常组织中 IGFBP6 mRNA 和蛋白的表达水平。此外，通过 CCK8 细胞计数试剂盒（CCK8）、集落形成和 Transwell 迁移实验探讨 IGFBP6 对细胞生长、迁移和侵袭的影响。我们还通过单因素和多因素分析探讨了肿瘤组织中 IGFBP6 表达与包括总生存期在内的各种临床参数的关系。
IGFBP6 mRNA 和蛋白水平在结直肠癌组织中均明显低于相邻正常结肠组织。使用 RNAi 下调 IGFBP6 可增加 CRC 细胞的增殖、迁移和侵袭。在单因素和多因素分析中，低 IGFBP6 表达均与较差的总生存期相关。
我们的数据表明，IGFBP6 可能在 CRC 的发生发展中发挥肿瘤抑制基因的作用，低 IGFBP6 表达可作为 CRC 的独立预后生物标志物。
