Comprehensive Analysis of Prognostic Value and Immune Infiltration of MMP12 in Esophageal Squamous Cell Carcinoma.

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.

Isoalantolactone induces apoptosis in human breast cancer cells via ROS-mediated mitochondrial pathway and downregulation of SIRT1.

Isoalantolactone possessed various biological activities. However, whether it could treat breast cancer and its underlying mechanism remained largely unknown. This study was designed to evaluate the anticancer effects of isoalantolactone on breast cancer and explored the molecular mechanism. Two human breast cancer cell lines (MDA-MB-231 and MCF-7) and one normal breast cell line (MCF-10A) were applied. Our data suggested that isoalantolactone decreased breast cancer cell viability in a dose-dependent manner, but showed almost no toxicity to MCF-10A cells. The anticancer effects of isoalantolactone were related to the overexpression of reactive oxygen species. Isoalantolactone significantly induced breast cancer cell apoptosis by activating caspase cascade, cleaving poly (ADP-ribose) polymerase. Increase of Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytoplasm and cell cycle arrest at G2/M phase were associated to the apoptosis induction. Additionally, isoalantolactone increased the protein expression of p38 MAPK and JNK. The apoptosis-induction of isoalantolactone could be abrogated by co-treatment with SB203580 (inhibitor of p38 MAPK) or SP600125 (inhibitor of JNK). Furthermore, isoalantolactone induced breast cancer cells apoptosis in a caspase-independent pathway, which was downregulation of SIRT1. Therefore, isoalantolactone may serve as a chemotherapeutic agent for the treatment of human breast cancer.

[Expression and clinical significance of Nrf2 in esophageal squamous cell carcinoma].

AIM: To study the expression and clinical significance of Nrf2 (Nuclear factor E2 p45-related factor 2) in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of Nrf2 in 32 cases of EC tissues, 30 cases of adjacent tissues, 21 positive Lymph node tissues and 24 negative Lymph node tissues was assessed by SP immunohistochemical method. RESULTS: The main location of Nrf2 was nuclear, and the positive rates of Nrf2 in the cancer tissues was 78.13%, while that in the adjacent tissues group was 13.33%, and showed 66.67% and 20.83% in the positive Lymph node tissues and negative Lymph node tissues respectively, there was a significant difference between the two groups (P<0.05). The Nrf2 positive rate was closely correlated with the lymph node metastasis (P<0.05), but showed no statistical associated with age, sex, TNM stage, degree of tumor differentiation and the location of tumor. CONCLUSION: The Nrf2 has high expression in ESCC tissues, and the positive rate is closely correlated with the lymph node metastasis, The Nrf2 may play an important role in ESCC oncogenesis and drug resistence.