Comprehensive analysis of the clinical and prognostic significance of SFRP1 and PRKCB expression in non-small cell lung cancer: a retrospective analysis.

OBJECTIVES: Secreted frizzled-related protein 1 (SFRP1) and protein kinase C-B (PRKCB) contribute to cancer progression and angiogenesis. This study intended to detect SFRP1 and PRKCB expression in non-small-cell lung cancer (NSCLC) patients and analyze its association with clinicopathological features. METHODS: A total of 108 NSCLC patients who underwent surgical resection in our hospital between 2012 and 2017 were retrospectively analyzed. SFRP1 and PRKCB expression was detected using immunohistochemical staining. The relationships between SFRP1 and PRKCB expression and clinicopathological data were analyzed using the chi-square method. Kaplan-Meier analysis was used to investigate survival probability over time. The potential risk of NSCLC morbidity associated with SFRP1 and PRKCB levels was analyzed using univariate and multivariate Cox proportional risk models. RESULTS: SFRP1 and PRKCB expression was negative in 114 and 109 of the 180 NSCLC specimens, respectively. SFRP1 expression was significantly associated with TNM stage ( P  < 0.001) and tumor diameter ( P  < 0.001). PRKCB expression was significantly associated with the TNM stage ( P  < 0.001). The correlation between SFRP1 and PRKCB expression was evident ( P  = 0.023). SFRP1(-) or PRKCB(-) patients shows lower survival rates than SFRP1(+) or PRKCB(+) patients ( P < 0.001). SFRP1(-)/PRKCB(-) patients had the worst prognosis ( P < 0.001). Furthermore, the mortality of SFRP1(-) or PRKCB(-) patients was significantly higher than that of SFRP1(+) or PRKCB(+). CONCLUSION: SFRP1 and PRKCB expression can be used to predict prognosis in patients with NSCLC.

High expression of Copine 1 promotes cell growth and metastasis in human lung adenocarcinoma.

Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients is poor. Further understanding of the disease mechanism and treatment strategies is required. Copines are a family of calcium-dependent phospholipid-binding proteins that are evolutionally conserved in various eukaryotic organisms and protists. Copine 1, encoded by CPNE1, is a soluble membrane-binding protein, which includes two tandem C2 domains at the N-terminus and an A domain at the C­terminus. A previous study reported that Copine 1 binds with various intracellular proteins via its A domain and C  omain. However, the role of CPNE1 in lung cancer remains unclear. In the presented study, CPNE1 expression level was demonstrated to be positively associated with the stage (P=0.002) and significantly associated with lymph node status (P=0.011) and distant metastasis (P=0.042). Furthermore, the function of CPNE1 in regulation of cell growth, migration and invasion was investigated, and it was demonstrated that knockdown of CPNE1 inhibits the cell cycle in NSCLC cells. Collectively, these data suggest that CPNE1 is an oncogene in NSCLC and serves an important role in tumorigenesis of NSCLC progression.

CPNE1 is a target of miR-335-5p and plays an important role in the pathogenesis of non-small cell lung cancer.

BACKGROUND: Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor. There is therefore a strong need to identify potential molecular targets for the treatment of NSCLC. In the present study, we investigated the function of CPNE1 in the regulation of cell growth, migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of CPNE1 and miR-335-5p. Western blot and immunohistochemical assays were used to investigate the levels of CPNE1 and other proteins. Flow cytometry was used to determine cell cycle stage and apoptosis. CCK-8 and clonogenic assays were used to investigate cell proliferation. Wound healing, migration and invasion assays were used to investigate the motility of cells. A lung carcinoma xenograft mouse model was used to investigate the in vivo effects of CPNE1 overexpression. RESULTS: We observed that knockdown of CPNE1 and increased expression of miR-335-5p inhibits cell proliferation and motility in NSCLC cells, and found that CPNE1 was a target of miR-335-5p. In addition, our data indicated that CPNE1 inhibition could improve the clinical effects of EGFR-tyrosine kinase inhibitors. CONCLUSIONS: The present results indicate that CPNE1 may be a promising molecular target in the treatment of NSCLC.

AGTR1 promoter hypermethylation in lung squamous cell carcinoma but not in lung adenocarcinoma.

Aberrant DNA methylation is associated with non-small cell lung cancer (NSCLC), suggesting that gene promoter methylation may be a potential biomarker for the detection or risk prediction of NSCLC. The present study aimed to evaluate the potential usage of angiotensin II receptor type 1 (AGTR1) methylation in two major pathologic subtypes: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Quantitative methylation-specific polymerase chain reaction was used to investigate the effect of AGTR1 promoter methylation in the tumor and the paired adjacent non-tumor tissue samples from 42 patients with LUSC, and 69 with LUAD. The percentage of methylated reference was calculated and presented as the median (interquartile range 25th-75th percentile). The results of the current study revealed that there was significantly increased AGTR1 promoter methylation in the tumor tissues compared with the paired adjacent non-tumor tissue [97.4 (57.22-130.5) vs. 85 (48.25-123); P=0.024]. Furthermore, higher AGTR1 promoter methylation was observed in patients with LUSC compared with LUAD (odds ratio=2.483; 95% confidence interval=1.125-5.480; P=0.023). Significant differences were identified in AGTR1 methylation between non-tumor and the tumor tissues in LUSC [113.5 (68.33-148.73) vs. 93.04 (45.94-140); P=0.008]. In addition, the Cancer Genome Atlas data of 378 patients with LUSC and 477 with LUAD revealed an inverse correlation between gene expression and the methylation status of AGTR1 promoter.. These data suggest that AGTR1 hypermethylation is a promising biomarker to assist in LUSC detection and diagnosis.

Diagnostic role of Wnt pathway gene promoter methylation in non small cell lung cancer.

Wnt signal pathway genes are known to be involved with cancer development. Here we tested the hypothesis whether DNA methylation of genes part of the Wnt signaling pathway could help the diagnosis of non-small cell lung cancer (NSCLC). The methylation levels of SFRP1, SFRP2, WIF1 and PRKCB in 111 NSCLC patients were evaluated by quantitative methylation-specific PCR (qMSP). Promoter methylation levels of four candidate genes were significantly higher in tumor tissues compared with the adjacent tissues. SFRP1, SFRP2 and PRKCB genes were all shown to be good predictors of NSCLC risk (SFRP1: AUC = 0.711; SFRP2: AUC = 0.631; PRKCB: AUC = 0.650). The combined analysis showed that the methylation status of the four genes had a sensitivity of 70.3% and a specificity of 73.9% in the prediction of NSCLC risk for study cohort. A higher diagnostic value with an AUC of 0.945 (95% CI: 0.923-0.967, sensitivity: 90.6%, specificity: 93.0%) was found in TCGA cohort. In addition, SFRP1 and SFRP2 hypermethylation events were specific to male patients. Further TCGA data mining analysis suggested that SFRP1_cg15839448, SFRP2_cg05774801, and WIF1_cg21383810 were inversely associated with the host gene expression. Moreover, GEO database analysis showed that 5'-Aza-deoxycytidine was able to upregulate gene expression in several lung cancer cell lines. Subsequent dual-luciferase reporter assay showed a crucial regulatory function of PRKCB promoter. In summary, our study showed that a panel of Wnt signal pathway genes (SFRP1, SFRP2, WIF1 and PRKCB) had the potential as methylation biomarkers in the diagnosis of NSCLC.

Genetic polymorphisms of interleukin-6 gene and susceptibility to coronary artery disease in Chinese population: Evidence based on 4582 subjects.

The aim of this study was to explore whether interleukin-6 (IL-6) gene (-174 G/C and -572 C/G) polymorphisms are associated with susceptibility to coronary artery disease (CAD) risk in Chinese population. All the statistical tests were performed using Stata version 11.0. Twelve articles involving 16 studies were included in this meta-analysis, covering a total of 2309 CAD cases and 2273 controls. For IL-6 gene -572 C/G polymorphism, the results showed evidence for significant association between IL-6 gene -572 C/G polymorphism and CAD risk (for G allele vs. C allele: OR=1.48, 95% CI=1.26-1.74, p<0.001; for G/G vs. C/C: OR=2.60, 95% CI=1.54-4.39, p<0.001; for G/G vs. G/C+C/C: OR=2.15, 95% CI=1.35-3.42, p=0.001; for G/G+G/C vs. C/C: OR=1.55, 95% CI=1.29-1.85, p<0.001). However, for IL-6 gene -174 G/C polymorphism, no significant association was found between this variation and CAD risk. In summary, our meta-analysis showed evidence that IL-6 gene -572 C/G polymorphism may be a risk factor for CAD susceptibility. For IL-6 gene -174 G/C polymorphism, no significant association was found between this variation and CAD risk.