Zhu Jing, Chen Rui, Mo Lijuan, Tang Haimei, Kuang Yeye, Fei Weiqiang, He Chao, Hu Xiaotong
Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province Hangzhou, China.
Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province Hangzhou, China ; Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University Hangzhou, China.
Am J Transl Res. 2015 Feb 15;7(2):339-47. eCollection 2015.
Fibulin-1, a multi-functional extracellular matrix protein, has been demonstrated to be involved in many kinds of cancer, while its function in colorectal cancer (CRC) is unclear. So here we investigated the expression and function of fibulin-1 in CRC. The expression of fibulin-1 mRNA variants named A, B, C and D in human colorectal cancer cells and colorectal cancer specimens were determined by RT-PCR. Fibulin-1 protein expression in colorectal cancer and normal colorectal mucosa tissue was evaluated by western blot, and was further validated by immunohistochemistry and enzyme-linked immunosorbent assay at serum level. The correlations between fibulin-1 expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method. Among fibulin-1 A-D variants, fibulin-1D is the predominant form expressed in colorectal cancer cell lines and colorectal cancer tissue, whereas only trace amounts of fibulin-1A-C were detectable. Fibulin-1 expressed higher in the CRC tissues and serum compared to normal control. So in the process of tumorigenesis of CRC, fibulin-1 is upregulated, however, high fibulin-1 expression showed longer survival time in colorectal cancer patients, especially in the patients with stage I/II. Low fibulin-1 expression was significantly associated with lymph node involvement, distant metastasis and Dukes' C and D stage (P < 0.05 for each). Fibulin-1 protein expression may be useful as a diagnosis and prognosis marker for colorectal cancer.
纤连蛋白-1是一种多功能细胞外基质蛋白,已被证明与多种癌症有关,但其在结直肠癌(CRC)中的功能尚不清楚。因此,我们在此研究了纤连蛋白-1在结直肠癌中的表达及功能。通过逆转录聚合酶链反应(RT-PCR)测定了人结肠癌细胞和结直肠癌标本中名为A、B、C和D的纤连蛋白-1 mRNA变体的表达。通过蛋白质免疫印迹法评估结直肠癌和正常结肠黏膜组织中纤连蛋白-1蛋白的表达,并通过免疫组织化学和血清水平的酶联免疫吸附测定进一步验证。通过卡方检验和费舍尔精确检验评估纤连蛋白-1表达与结直肠癌临床病理特征之间的相关性。采用Kaplan-Meier法计算生存率。在纤连蛋白-1的A-D变体中,纤连蛋白-1D是在结肠癌细胞系和结直肠癌组织中表达的主要形式,而仅可检测到微量的纤连蛋白-1A-C。与正常对照相比,纤连蛋白-1在结直肠癌组织和血清中的表达更高。因此,在结直肠癌的肿瘤发生过程中,纤连蛋白-1上调,然而,高纤连蛋白-1表达在结直肠癌患者中显示出更长的生存时间,尤其是在I/II期患者中。低纤连蛋白-1表达与淋巴结受累、远处转移以及Dukes' C和D期显著相关(每项P < 0.05)。纤连蛋白-1蛋白表达可能作为结直肠癌的诊断和预后标志物。