Abstract：
Hepatocellular carcinoma (HCC) remains an incurable malignancy despite the treatment methods being continually updated. Matrix metalloproteinases (MMPs) promote the progression of HCC; however, no consensus exists on which MMP plays the predominant role in HCCs. In the present study, we analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the Cancer Genome Atlas database. The KEGG enrichment pathway using differentially expressed genes included extracellular matrix-receptor interaction, which was correlated with MMPs. We found that among the MMP family, only MMP1, MMP3, MMP8, MMP9, MMP11, MMP12, MMP14, MMP15, MMP20, MMP21, and MMP24 significantly increased in HCCs compared with adjacent tissues. Crucially, survival and univariate analyses indicated that only MMPs 1, 9, 12, and 14 predict poor overall survival; however, multivariate Cox analysis and a nomogram demonstrated that only MMP1 is a poor prognostic biomarker for HCCs. In addition, we observed significant enrichment of uncharacterized cells but decreased macrophages in HCC tissues. Consistent with decreased macrophages in HCCs, MMP1 was negatively associated with macrophages but positively correlated with uncharacterized cells, indicating that the main producer of MMP1 is uncharacterized cells. Furthermore, MMP1 expression was negatively correlated with immune responses of HCCs. Taken together, our findings indicated that MMP1 is a poor and predominant prognostic biomarker for patients with HCC and that anti-MMP1 may be a novel therapy that is worth studying in depth.
摘要：
尽管治疗方法不断更新，但肝细胞癌（HCC）仍然是无法治愈的恶性肿瘤。基质金属蛋白酶（MMPs）促进HCC的进展；然而，关于MMP在HCC中起主要作用尚无共识。在本研究中,我们分析了肝癌中差异表达的基因，尤其是MMPs,使用癌症基因组图谱数据库与邻近组织进行比较。使用差异表达基因的KEGG富集途径包括细胞外基质-受体相互作用，与MMP相关。我们发现在MMP家族中,与邻近组织相比，只有MMP1，MMP3，MMP8，MMP9，MMP11，MMP12，MMP14，MMP15，MMP20，MMP21和MMP24显着增加。至关重要的是，生存和单变量分析表明，只有MMPs1、9、12和14预测总体生存较差；多变量Cox分析和列线图表明，只有MMP1是HCC的不良预后生物标志物。此外,我们观察到未表征的细胞显着富集，但在HCC组织中巨噬细胞减少。与HCC中巨噬细胞减少一致，MMP1与巨噬细胞呈负相关，但与未表征的细胞呈正相关，表明MMP1的主要生产者是未表征的细胞。此外，MMP1的表达与肝癌的免疫反应呈负相关。一起来看,我们的研究结果表明,MMP1是HCC患者预后不良的主要生物标志物,抗MMP1可能是一种值得深入研究的新疗法.
