Jin Mei, Long Zi-Wen, Yang Jing, Lin Xiang
Department of Surgery, Shigatse People's Hospital, Shigatse, Tibet, 85700, People's Republic of China.
Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.
Pathol Oncol Res. 2018 Jan;24(1):45-57. doi: 10.1007/s12253-017-0195-5. Epub 2017 Feb 10.
This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RT-qPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and K-Ras in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.
本病例对照研究旨在探讨胰岛素样生长因子受体1（IGF-1R）和环氧合酶2（COX-2）表达与Ras和BRAF基因突变、结直肠癌（CRC）患者临床病理特征及预后的相关性。从我院选取了213例CRC患者（病例组）和200例健康个体（对照组）。通过直接测序检测Ras（K-Ras/N-Ras）和BRAF基因突变。采用免疫组织化学检测CRC组织和正常组织中IGF-IR和COX-2的阳性表达率。应用RT-qPCR和蛋白质印迹法检测CRC组织和正常组织中IGF-IR和COX-2的mRNA和蛋白表达。病例组中N-Ras、BRAF和K-Ras总突变率分别为5.2%、12.2%和47.4%。Ras和BRAF基因突变的CRC组织中IGF-IR和COX-2的表达高于无突变者。Ras突变的CRC组织中COX-2表达高于BRAF突变者。IGF-IR和COX-2表达与浸润程度、淋巴转移（无论有无Ras和BRAF基因突变的CRC组织）及Dukes分期（仅在有Ras和BRAF基因突变的CRC组织中）相关。IGF-IR和COX-2表达阴性的CRC患者累积生存率显著高于表达阳性者，平均生存时间更长。这些发现表明，IGF-1R和COX-2表达可能与Ras and BRAF基因突变、CRC患者临床病理特征及预后相关。
