Department of Gastrointestinal Surgery, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China.
Department of Gastrointestinal Surgery, The First People's Hospital of Shangqiu, Shangqiu 476100, Henan Province, China.
Hum Pathol. 2019 Jan;83:36-42. doi: 10.1016/j.humpath.2018.03.030. Epub 2018 Aug 16.
Matrix metalloproteinases (MMPs) are involved in most biological processes. Recently, MMP14 was reported to be up-regulated in some types of cancer and to promote cancer cell invasion and metastasis. However, there are few reports on the clinical significance of MMP14 in colorectal cancer (CRC). In this study, MMP14 expression was first investigated in The Cancer Genome Atlas (TCGA) and whole-genome expression microarray (GEO; Accession Number GSE39582) and then validated with our database. Univariate and multivariate analyses were performed to assess the association between prognostic factors and survival outcomes. MMP14 was upregulated at both the transcriptional and protein levels in cancer compared with normal tissues (P < .05), and high MMP14 expression was associated with advanced tumor stage in the 3 study cohorts. In the univariate Cox proportional hazard ratio analysis, MMP14 correlated significantly with prognosis in both the TCGA and GSE39582 databases (P < .05). In the validation cohort, patients with high MMP14 expression had lower 5-year disease-free survival (DFS; hazard ratio [HR] 6.707; 95% confidence interval [CI] 3.184, 14.128; P < .001) and overall survival (OS; HR 10.669; 95% CI 3.828, 29.737; P < .001) than those with low MMP14 expression. Multivariate survival analysis showed that MMP14 was an independent prognostic marker for both DFS (HR 5.776; 95% CI 2.719, 12.270; P < .001) and OS (HR 8.971; 95% CI 3.199, 25.156; P < .001). Clearly, MMP14 plays an important role in CRC progression and prognosis and could be a useful biomarker for prediction of survival after colectomy.
基质金属蛋白酶(MMPs)参与了大多数生物学过程。最近,有报道称 MMP14 在某些类型的癌症中上调,并促进癌细胞的侵袭和转移。然而,关于 MMP14 在结直肠癌(CRC)中的临床意义的报道很少。在本研究中,首先在癌症基因组图谱(TCGA)和全基因组表达微阵列(GEO;注册号 GSE39582)中研究了 MMP14 的表达,然后用我们的数据库进行了验证。进行单变量和多变量分析以评估预后因素与生存结果之间的关系。与正常组织相比,癌症组织中 MMP14 的转录和蛋白水平均上调(P<0.05),并且在 3 个研究队列中,高 MMP14 表达与肿瘤晚期相关。在单变量 Cox 比例风险比分析中,TCGA 和 GSE39582 数据库中 MMP14 与预后显著相关(P<0.05)。在验证队列中,高 MMP14 表达的患者 5 年无病生存率(DFS;危险比[HR]6.707;95%置信区间[CI]3.184,14.128;P<0.001)和总生存率(OS;HR 10.669;95%CI 3.828,29.737;P<0.001)均低于低 MMP14 表达的患者。多变量生存分析显示,MMP14 是 DFS(HR 5.776;95%CI 2.719,12.270;P<0.001)和 OS(HR 8.971;95%CI 3.199,25.156;P<0.001)的独立预后标志物。显然,MMP14 在 CRC 的进展和预后中起重要作用,并且可能是预测结肠切除术后生存的有用生物标志物。