ABSTRACT
Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether RRM2 gene expression is associated with the prognosis of patients with lung adenocarcinoma (LUAD) using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RRM2 expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of RRM2 expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the RRM2 gene expression and the risk of LUAD. TCGA data set was used for gene set enrichment analysis (GSEA). We also performed a further experiment in vitro to assess the effect of RRM2 expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of RRM2 in patients with LUAD was much higher than that in normal tissues (p = 3.99e-32). High expression of RRM2 was significantly associated with tumor stage (IV vs. I: OR = 3.02, p = 0.012) and TNM classification (T2 vs. T1: OR = 1.88, p = 0.001; N2 vs. N0: OR = 2.69, p < 0.001). Kaplan-Meier survival analysis showed that high expression of RRM2 was associated with a worse prognosis of LUAD compared low expression of RRM2 (p = 7.86e-04). Multivariate analysis showed that high RRM2 expression was an independent factor affecting overall survival (HR = 1.29, p < 0.001). The association between RRM2 gene expression and the risk of LUAD was presented in a nomogram. GSEA revealed that the cell cycle, p53 signaling pathway, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially enriched in patients with high expression of RRM2. RRM2 over-expression promoted the proliferation and invasive abilities of LUAD cells. RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Ribonucleoside Diphosphate Reductase , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/pathology , Aged , Cell Cycle/genetics , Cell Line , Female , Humans , Lung/metabolism , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Ribonucleoside Diphosphate Reductase/analysis , Ribonucleoside Diphosphate Reductase/genetics , Ribonucleoside Diphosphate Reductase/metabolism , Signal Transduction/geneticsABSTRACT
This study was to investigate inhibiting effect of structurally unique Second mitochondria-derived activator of caspase (Smac) in combination with Docetaxel on lung cancer cell line A549. Results showed that the expression of Smac in transfected A549 cells was higher than the control cells both at mRNA level and protein level (P<0.05). Smac over-expression induced a little apoptosis, however, when treated with Docetaxel together, the cells showed a higher apoptosis rate. The apoptosis rate was significantly increased in Smac + Docetaxel group when compared with that in Smac group and Docetaxel group (P<0.05). Cells cloning ability in Smac + Docetaxel group was worse than that of other groups (P<0.05), cell mass formed in relatively small quantities and sparse location. Thus, over-expression of Smac increases the sensitivity of lung cancer A549 cells to Docetaxel treatment, and transfection of Smac to tumor cells might provide a potential therapy modality.
ABSTRACT
We introduce and study some types of fuzzy prefilters (filters) in EQ-algebras. First, we present several characterizations of fuzzy positive implicative prefilters (filters), fuzzy implicative prefilters (filters), and fuzzy fantastic prefilters (filters). Next, using their characterizations, we mainly consider the relationships among these special fuzzy filters. Particularly, we find some conditions under which a fuzzy implicative prefilter (filter) is equivalent to a fuzzy positive implicative prefilter (filter). As applications, we obtain some new results about classical filters in EQ-algebras and some related results about fuzzy filters in residuated lattices.
