He Min-Ke, Le Yong, Zhang Yong-Fa, Ouyang Han-Yue, Jian Pei-En, Yu Zi-Shan, Wang Li-Juan, Shi Ming
Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China.
Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, P.R. China.
Oncol Lett. 2018 Jul;16(1):475-482. doi: 10.3892/ol.2018.8642. Epub 2018 May 4.
Hepatocellular carcinoma (HCC) is among the most fatal types of cancer worldwide due to its high rates of recurrence and metastasis. The molecular processes involved in HCC progression require further investigation to identify biomarkers for use in diagnosis and treatment. In the present study, the significance and prognostic value of matrix metallopeptidase 12 (MMP12) expression in human HCC was investigated. MMP12 mRNA expression was investigated using reverse transcription-quantitative polymerase chain reaction analysis of 42 pairs of tumor and non-tumor liver tissues obtained from patients with HCC following surgical treatment. Immunohistochemical staining was used to detect MMP12 and forkhead box P3 (FOXP3) expression in 158 paraffin-embedded HCC tissues. The prognostic value of MMP12 expression was determined using Kaplan-Meier analysis and the Cox proportional hazards model. MMP12 mRNA levels were significantly higher in liver tumor tissues compared with matched non-tumor liver tissues. MMP12 expression and FOXP3 regulatory T cell (Treg) infiltration was positively correlated (r=0.302; P<0.001). MMP12 protein overexpression was positively correlated with tumor size (P=0.018), high serum alpha-fetoprotein levels (P=0.005) and poor overall survival time (P=0.012) in patients with HCC. Furthermore, MMP12 protein level was an independent predictive factor for overall survival time of patients with HCC who underwent curative resection. In conclusion, these results suggest that MMP12 may increase FOXP3 Treg infiltration into tumor tissues, and promote tumor progression and immune evasion of HCC. The overexpression of MMP12 protein is, therefore, a valuable prognostic indicator in patients with HCC.
肝细胞癌（HCC）是全球最致命的癌症类型之一，因其高复发率和转移率。HCC进展所涉及的分子过程需要进一步研究以确定用于诊断和治疗的生物标志物。在本研究中，调查了基质金属肽酶12（MMP12）在人类HCC中的表达意义和预后价值。使用逆转录定量聚合酶链反应分析对42对手术治疗后HCC患者的肿瘤和非肿瘤肝组织进行MMP12 mRNA表达研究。免疫组织化学染色用于检测158例石蜡包埋的HCC组织中MMP12和叉头框P3（FOXP3）的表达。使用Kaplan-Meier分析和Cox比例风险模型确定MMP12表达的预后价值。与匹配的非肿瘤肝组织相比，肝肿瘤组织中MMP12 mRNA水平显著更高。MMP12表达与FOXP3调节性T细胞（Treg）浸润呈正相关（r = 0.302；P < 0.001）。HCC患者中MMP12蛋白过表达与肿瘤大小（P = 0.018）、高血清甲胎蛋白水平（P = 0.005）和总体生存时间差（P = 0.012）呈正相关。此外，MMP12蛋白水平是接受根治性切除的HCC患者总体生存时间的独立预测因素。总之，这些结果表明MMP12可能增加FOXP3 Treg浸润到肿瘤组织中，并促进HCC的肿瘤进展和免疫逃逸。因此，MMP12蛋白的过表达是HCC患者有价值的预后指标。
