Lung cancer is the most common malignancy worldwide. Thus, there is a critical need for diagnostic biomarkers with adequate sensitivity and specificity for lung cancer detection. Glycans in glycoproteins are significantly altered in cancer, and may serve as a tool for identifying potential diagnostic biomarkers. Recent studies have reported changes in α-1-antitrypsin (A1AT) glycosylation in lung cancer serum, tissue and cell lines. In this study, a lectin microarray was used to detect glycosylation changes in serum A1AT from patients with lung adenocarcinoma (ADC), squamous cell lung cancer, small-cell lung cancer (SCLC) and benign pulmonary diseases. Differentially expressed glycosylated patterns of A1AT were identified by lectin arrays and were confirmed by lectin-based enzyme-linked immunosorbent assay (ELISA). We found that galactosylated A1AT could distinguish non-small-cell lung cancer (NSCLC) from benign pulmonary diseases (AUC = 0.834); fucosylated A1AT showed exceptional capability in distinguishing ADC from benign diseases (AUC = 0.919) or other lung cancer subtypes (AUC = 0.844), and A1AT containing poly-LacNAc could detect SCLC from benign diseases (AUC = 0.905) or NSCLC (AUC = 0.707). The present study indicates that glycosylated patterns of A1AT may serve as potential biomarkers for detection of lung cancer. Further studies in larger sample sizes are necessary to validate the clinical utility of these markers.
A salt substitute containing potassium and calcium was as effective as sodium restriction in reducing BP in hypertensive adolescents and their families in a that rural Chinese community.
MicroRNAs (miRNAs) play a critical role in cancer development and progression. Aberrant expression of miR-15a has recently been reported in several cancers, but its role in non-small cell lung cancer (NSCLC) still remains obscure. We investigated the effects of miR-15a on proliferation, apoptosis, and metastasis in A549 cells. Eighteen paired NSCLC and adjacent non-tumor lung tissues were surgically removed and immediately snap frozen until total RNA was extracted and confirmed by two independent pathologists. The targets of miR-15a were predicted by bioinformatics tools. RNA isolation and quantitative real-time PCR (qRT-PCR), Western blot analysis, cell proliferation assay, cell cycle analysis, cell apoptosis assay, and migration and invasion assays were done. The wild type (WT) or mutant type (MT) 3'-untranslated region (UTR) vectors were co-transfected with miR-15a or negative control into A549 cells, and after 24 h of transfection, luciferase activity was measured using the Dual-Glo luciferase assay kit. Statistical analysis was performed using SPSS 13.0 software (SPSS, Chicago, IL, USA). P values of less than 0.05 were considered statistically significant. miR-15a was significantly downregulated in NSCLC than in adjacent non-cancerous tissues. miR-15a overexpression remarkably inhibited cell viability, invasion, and migration and promoted the apoptosis of NSCLC cells. Additionally, inhibition of miR-15a expression had the opposite effects on tumor progression, while cell cycle remained unaltered. Furthermore, we identified that BCL2L2 was a target of miR-15a and negatively regulated by miR-15a at the translational level. miR-15a acts as a tumor suppressor in NSCLC by directly targeting BCL2L2 and may serve as a potential diagnostic biomarker and therapeutic target for NSCLC.
Lung cancer has the highest mortality rate among cancers; however, its nosogenesis is still unclear. Genome-wide association studies have shown that the telomerase reverse transcriptase (TERT) gene, located in the chromosome 5p15.33 region, is one of the genes associated with the risk of lung cancer. In this case-control study, we genotyped 11 tag single-nucleotide polymorphisms of the TERT gene to evaluate their association with lung cancer risk in the Han Chinese population. Two tag single-nucleotide polymorphisms were found to be associated with lung cancer risk on using the χ2-test: rs4246742 [odds ratio (OR)=0.77, 95% confidence interval (CI) 0.60-0.98; P=0.03] and rs2853672 (OR=1.26, 95% CI 1.01-1.57; P=0.045). By using SNPStats software we also found rs2242652 (OR=1.47, 95% CI 1.02-2.13; P=0.04) in the dominant model and rs2736098 (OR=1.38, 95% CI 1.06-1.80; P=0.017), rs2853672 (OR=1.41, 95% CI 1.11-1.80; P=0.0048), and rs4246742 (OR=0.75, 95% CI 0.58-0.97; P=0.029) in the log-additive model. 'T/C-T/T' of rs10069690 conferred an increased risk for male sex in the dominant model (OR=1.80, 95% CI, 1.05-3.08; P=0.03) and 'TC' increased risk for male sex in the overdominant model (OR=1.85, 95% CI, 1.08-3.17; P=0.031). Our findings, combined with previous studies, suggest that polymorphisms in the TERT gene contribute to the risk for lung cancer in the Chinese Han population.
Background Lung cancer is the leading cause of cancer death in China and around the world. Early detection is key to improving the survival rate of non-small cell lung cancer (NSCLC). Alteration in glycosylation has been observed in cancers, and glycans can be a source for the development of new biomarkers for NSCLC. Methods In this glycan biomarker discovery study, we measured serum N - and O -glycan profiles in NSCLC patients with different stages and healthy controls by performing lectin microarray analysis. The alterations of serum glycopatterns were compared between NSCLC patients and controls, and the stage-related changes in serum glycosylation were evaluated. Results There were 18 lectins (e.g., AAL, Jacalin, GSL-I and DBA) to give significantly alterations of serum glycopatterns in lung adenocarcinoma compared with control group. Meanwhile, 16 lectins (e.g., Jacalin, HHL, and PHA-E+L) exhibited significantly alterations of serum glycopatterns in squamous cell carcinoma (SCC) compared with control group. Importantly, most of the lectins showing altered signals exhibited significantly increased or decreased NFIs in patients with early stage adenocarcinoma and SCC. Conclusions The serum glycan profiles were significantly different between NSCLC and healthy control, and most of the glycosylation changes had occurred at early stage. Further evaluation is needed to examine the diagnostic value of the glycan markers identified in this study. Electronic supplementary material The online version of this article (10.1186/s12014-019-9240-6) contains supplementary material, which is available to authorized users.
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