Prognostic value of MMP9 activity level in resected stage I B lung adenocarcinoma

Molecular Carcinogenesis

et al. 2017

Metzincins are key molecules in the degradation of the extracellular matrix and play an important role in cellular processes such as cell migration, adhesion, and cell fusion of malignant tumors, including cutaneous melanoma (CM). We hypothesized that genetic variants of the metzincin metallopeptidase family genes would be associated with CM-specific survival (CMSS). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate the associations between genetic variants of 75 metzincin metallopeptidase family genes and CMSS using the dataset from the genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC) which included 858 non-Hispanic white patients with CM, and then validated using the dataset from the Harvard GWAS study which had 409 non-Hispanic white patients with invasive CM. Four independent SNPs (MMP16 rs10090371 C>A, ADAMTS3 rs788935 T>C, TLL2 rs10882807 T>C and MMP9 rs3918251 A>G) were identified as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) of 1.73 (1.32-2.29, 9.68E-05), 1.46 (1.15-1.85, 0.002), 1.68 (1.31-2.14, 3.32E-05) and 0.67 (0.51-0.87, 0.003), respectively, in the meta-analysis of these two GWAS studies. Combined analysis of risk genotypes of these four SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (P < 0.001). An improvement was observed in the prediction model (area under the curve [AUC] = 81.4% vs. 78.6%), when these risk genotypes were added to the model containing non-genotyping variables. Our findings suggest that these genetic variants may be promising prognostic biomarkers for CMSS.

Section: Discussionmentioning

confidence: 99%

Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival

Wang

Molecular Carcinogenesis

et al. 2017

“…Despite improvements in the detection and treatment of early‐stage lung cancer, which may be a result of the increased use of computed tomography (CT), a third of patients with early‐stage lung cancer survive less than five years . This is partially attributable to the limited therapeutic efficacy of surgery, radiation, and chemotherapy in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Newcastle disease virus expressing human IFN‐λ1 (rL‐hIFN‐λ1)‐induced apoptosis of A549 cells is connected to endoplasmic reticulum stress pathways

Yan

et al. 2018

Thoracic Cancer

BackgroundIFN‐λs are a kind of cytokine with anti‐tumor, immunomodulatory, and anti‐proliferative activity. Recent studies have shown that the recombinant Newcastle disease virus expresses human IFN‐λ1 (rL‐hIFN‐λ1), which plays a role in gastric cancer cell apoptosis. Endoplasmic reticulum stress (ERS) induces autophagy and apoptosis in tumor cells. In this study, we explored the relationship between ERS and rL‐hIFN‐λ1‐induced apoptosis of lung adenocarcinoma A549 cells and its underlying mechanism.MethodsFirst, we investigated the effect of rL‐hIFN‐λ1 on cellular proliferation, migration, and proteins associated with ERS, autophagy, and apoptosis of A549. Second, after administration of the ERS inhibitor, the associated proteins induced by rL‐hIFN‐λ1 were detected. Finally, a subcutaneous mouse model was used to examine the effect of rL‐hIFN‐λ1 on tumor growth and the ERS and apoptosis associated proteins in tumor tissues.ResultsThe results showed that the proliferation and migration of A549 cells, and tumor tissue growth were significantly inhibited and the ERS, autophagy, and apoptosis associated proteins were upregulated in the experimental group. Additionally, both 4‐PBA and knockdown of PERK or CHOP reduced the levels of rL‐hIFN‐λ1‐induced autophagy and apoptosis‐associated proteins. BCL‐2 knockdown caused autophagy and apoptosis associated protein upregulation.ConclusionsIn summary, rL‐hIFN‐λ1 inhibited cell proliferation and activated ERS, autophagy, and apoptosis in A549 cells and tissues, and when ERS pathways were blocked, the inhibiting effect was even more pronounced. Therefore, the recombinant Newcastle disease virus rL‐hIFN‐λ1‐induced apoptosis of A549 cells is connected to ER stress and could be a promising therapeutic agent for lung adenocarcinoma.

“…Association between PKCζ, MMP-2 and MMP-9 expression in lung adenocarcinoma. angiogenesis, invasion and metastasis (26,27). The mechanism underlying this effect involves the increase of VEGF secretion from tumor cells induced by MMP-2 and MMP-9, promoting invasion and metastasis, which is dependent on MAPK activation and ERK phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

PKCζ, MMP-2 and MMP-9 expression in lung adenocarcinoma and association with a metastatic phenotype

Cai

Zhu

Molecular Medicine Reports

2017

The aim of the present study was to investigate protein kinase C ζ type (PKCζ), matrix metalloproteinase (MMP)‑2 and MMP‑9 expression in lung adenocarcinoma and to define their association with in vitro invasion and metastatic capacity. PKCζ, MMP‑2 and MMP‑9 expression was assessed by immunohistochemistry in 110 cases of lung adenocarcinoma. PKCζ small interfering (si)RNA was transfected into A549 cells, and western blotting was used to confirm PKCζ‑knockdown in transfected cells and to measure MMP‑2 and MMP‑9 levels. A Transwell invasion assay was used to detect in vitro invasive capacity. The rates of positive PKCζ, MMP‑2 and MMP‑9 staining in lung adenocarcinoma tissues were 52.73, 55.45 and 61.82%, respectively. PKCζ expression was increased in malignant tissues compared with adjacent normal lung tissues and was associated with lymph node metastasis (P<0.05), although it was not associated with any other clinicopathological parameters, including sex, age, tumor size, smoking status or distant metastases (all P>0.05). PKCζ, MMP‑2 and MMP‑9 expression was markedly decreased in siPKCζ‑treated A549 cells, which exhibited a significantly decreased invasive capacity in the Transwell invasion assay (P<0.05). In conclusion, PKCζ promoted lung adenocarcinoma invasion and metastasis, and its expression was associated with MMP‑2 and MMP‑9 expression. PKCζ may be a potential target for gene therapy in lung adenocarcinoma.