Department of General Surgery, The Affiliated Hospital of Nantong University, No. 20, Xisi Rd, Nantong 226001, People's Republic of China.
J Gastrointest Surg. 2011 Jul;15(7):1205-12. doi: 10.1007/s11605-011-1546-2. Epub 2011 May 12.
The aims of this study were to investigate metastasis suppressor 1 (MTSS1) expression in benign and malignant colorectal tissues and to explore its significance in the prognosis of colorectal cancer (CRC) patients.
MTSS1 expression was detected by immunohistochemistry in CRC, colorectal adenomatous polyp (precancerous lesion) and normal colorectal tissues. The relationship between MTSS1 expression in CRC tissues and clinicopathologic factors was analyzed with Mann-Whitney U test. MTSS1 protein expression was observed by Western blot in CRC tissues and adjacent nontumor colorectal tissues. Two factors between MTSS1 expression and CRC patient tumor node metastasis (TNM) stage were analyzed by Spearman rank correlation analysis. The Kaplan-Meier method and log-rank test were employed to compare the overall survival between MTSS1 negative/weak positive expression group and MTSS1 strong positive expression group.
MTSS1 expression rates were significantly higher in CRC tissues (99 out of 135, 73.30%) than that in normal colorectal tissues (one out of seven, 14.29%), nontumor colorectal tissues (six out of 32, 18.75%), and adenomatous polyp tissues (four out of 15, 26.67%; P = 0.003, P < 0.001, P = 0.001, respectively). The upregulated MTSS1 expression in CRC tissues was significantly correlated to poor differentiation (P = 0.005), tissue invasion (P = 0.018), high preoperative CEA level (P = 0.022), present lymph node metastasis (P = 0.003), and high TNM stage (P = 0.002). MTSS1 expression was positively correlated with clinical TNM stage, that suggested the more advanced clinical TNM stage corresponding to the higher expression level of MTSS1 (r(s) = 0.327, P < 0.05). Western blotting demonstrated that MTSS1 expression was upregulated in 25 of 32 CRC tissues (75.0%) compared to corresponding adjacent nontumor colorectal tissues. The overall 5-year survival of MTSS1 strong positive expression CRC patients was significantly shorter than that of MTSS1 negative and weakly positive expression group. In multivariate analysis, MTSS1 expression maintained independent prognostic influence on overall survival (P = 0.004).
MTSS1 may be a good biomarker to be applied in the clinical setting to predict the prognosis of CRC patients with completely resected.
本研究旨在探讨转移抑制因子 1（MTSS1）在良性和恶性结直肠组织中的表达，并探讨其在结直肠癌（CRC）患者预后中的意义。
采用免疫组织化学法检测 CRC、结直肠腺瘤性息肉（癌前病变）和正常结直肠组织中 MTSS1 的表达。采用 Mann-Whitney U 检验分析 CRC 组织中 MTSS1 表达与临床病理因素的关系。采用 Western blot 法观察 CRC 组织和相邻非肿瘤结直肠组织中 MTSS1 蛋白的表达。采用 Spearman 秩相关分析两种因素与 CRC 患者肿瘤淋巴结转移（TNM）分期的关系。采用 Kaplan-Meier 法和对数秩检验比较 MTSS1 阴性/弱阳性表达组和 MTSS1 强阳性表达组的总生存率。
CRC 组织中 MTSS1 表达率（99/135，73.30%）显著高于正常结直肠组织（1/7，14.29%）、非肿瘤结直肠组织（6/32，18.75%）和腺瘤性息肉组织（4/15，26.67%）（P=0.003，P<0.001，P=0.001）。CRC 组织中 MTSS1 的上调表达与分化不良（P=0.005）、组织浸润（P=0.018）、术前 CEA 水平升高（P=0.022）、淋巴结转移（P=0.003）和较高的 TNM 分期（P=0.002）显著相关。MTSS1 表达与临床 TNM 分期呈正相关，提示临床 TNM 分期越高，MTSS1 表达水平越高（r(s)=0.327，P<0.05）。Western blot 显示，与相应的非肿瘤结直肠组织相比，25/32（75.0%）CRC 组织中 MTSS1 表达上调。MTSS1 强阳性表达的 CRC 患者的总 5 年生存率明显短于 MTSS1 阴性和弱阳性表达组。多因素分析显示，MTSS1 表达对总生存仍具有独立的预后影响（P=0.004）。
MTSS1 可能是一种很好的生物标志物，可应用于临床预测完全切除的 CRC 患者的预后。
