Mao Jing-Tao, Lu Qiang, Jing Peng-Yu, Li Zi-Liang, Yang Xiao-Qi, Zhang Ji-Peng, Li Zhe
Department of Thoracic Surgery, Shaanxi Provincial Sengong Hospital, Xi'an, Shaanxi 710300, China.
Department of Thoracic Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, Shaanxi 710038, China.
J Oncol. 2022 Feb 27;2022:4097428. doi: 10.1155/2022/4097428. eCollection 2022.
Esophageal squamous cell carcinoma (ESCC) is a typical neoplastic disease and a frequent cause of death in China. The prognosis of most ESCC patients is still poor. Previous studies demonstrated that MMP12 is involved in tumor metastasis. However, its clinical significance and association with cancer immunity remained largely unclear. In this study, we first analyzed the expressing pattern of MMPs in ESCC from TCGA datasets and found that several MMPs expression was distinctly increased in ESCC. However, only MMP12 expression was associated with five-year survival of ESCC patients. Then, we focused on MMP12 and found its high expression was positively related to advanced clinical stages of ESCC specimens. KEGG assays revealed MMP12 may influence the activity of several tumor-related pathways, such as the Toll-like receptor signaling pathway, TNF signaling pathway, and IL-17 signaling pathway. Then, we sought to determine whether MMP12 expressions were related to immune cell infiltration in ESCC. We observed that increased MMP12 levels were positively associated with the infiltration levels of mast cells activated and macrophages M0. However, eosinophils, B cells naïve, and mast cells resting exhibited an opposite result. Finally, we showed that knockdown of MMP12 suppressed the proliferation of ESCC cells. Overall, our findings proved that high expression of MMP12 may be a novel and valuable prognostic factor in ESCC.
食管鳞状细胞癌（ESCC）是一种典型的肿瘤性疾病，也是中国常见的死亡原因。大多数ESCC患者的预后仍然很差。先前的研究表明，MMP12参与肿瘤转移。然而，其临床意义以及与癌症免疫的关联在很大程度上仍不清楚。在本研究中，我们首先从TCGA数据集中分析了ESCC中MMPs的表达模式，发现几种MMPs在ESCC中的表达明显增加。然而，只有MMP12的表达与ESCC患者的五年生存率相关。然后，我们聚焦于MMP12，发现其高表达与ESCC标本的临床晚期呈正相关。KEGG分析显示，MMP12可能影响几种肿瘤相关通路的活性，如Toll样受体信号通路、TNF信号通路和IL-17信号通路。然后，我们试图确定MMP12的表达是否与ESCC中的免疫细胞浸润有关。我们观察到MMP12水平的升高与活化肥大细胞和M0巨噬细胞的浸润水平呈正相关。然而，嗜酸性粒细胞、未成熟B细胞和静止肥大细胞则呈现相反的结果。最后，我们表明敲低MMP12可抑制ESCC细胞的增殖。总体而言，我们的研究结果证明，MMP12的高表达可能是ESCC中一种新的有价值的预后因素。
