Osteosarcoma transcriptome data exploration reveals STC2 as a novel risk indicator in disease progression.

BACKGROUND: Osteosarcoma has been the most common primary bone malignant tumor in children and adolescents. Despite the considerable improvement in the understanding of genetic events attributing to the rapid development of molecular pathology, the current information is still lacking, partly due to the comprehensive and highly heterogeneous nature of osteosarcoma. The study is to identify more potential responsible genes during the development of osteosarcoma, thus identifying promising gene indicators and aiding more precise interpretation of the disease. METHODS: Firstly, from GEO database, osteosarcoma transcriptome microarrays were used to screen the differential expression genes (DEGS) in cancer comparing to normal bone samples, followed by GO/KEGG interpretation, risk score assessment and survival analysis of the genes, for the purpose of selecting a credible key gene. Further, the basic physicochemical properties, predicted cellular location, gene expression in human cancers, the association with clinical pathological features and potential signaling pathways involved in the key gene's regulation on osteosarcoma development were in succession explored. RESULTS: Based on the selected GEO osteosarcoma expression profiles, we identified the differential expression genes in osteosarcoma versus normal bone samples, and the genes were classified into four groups based on the difference level, further genes interpretation indicated that the high differently level (> 8 fold) genes were mainly located extracellular and related to matrix structural constituent regulation. Meanwhile, module function analysis of the 67 high differential level (> 8 fold) DEGS revealed a 22-gene containing extracellular matrix regulation associated hub gene cluster. Further survival analysis of the 22 genes revealed that STC2 was an independent prognosis indicator in osteosarcoma. Moreover, after validating the differential expression of STC2 in cancer vs. normal tissues using local hospital osteosarcoma samples by IHC and qRT-PCR experiment, the gene's physicochemical property revealed STC2 as a cellular stable and hydrophilic protein, and the gene's association with osteosarcoma clinical pathological parameters, expression in pan-cancers and the probable biological functions and signaling pathways it involved were explored. CONCLUSION: Using multiple bioinformatic analysis and local hospital samples validation, we revealed the gain of expression of STC2 in osteosarcoma, which associated statistical significantly with patients survival, and the gene's clinical features and potential biological functions were also explored. Although the results shall provide inspiring insights into further understanding of the disease, further experiments and detailed rigorous clinical trials are needed to reveal its potential drug-target role in clinical medical use.

Bioinformatic analysis revealing mitotic spindle assembly regulated NDC80 and MAD2L1 as prognostic biomarkers in non-small cell lung cancer development.

BACKGROUND: Lung cancer has been the leading cause of tumor related death, and 80% ~ 85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. METHODS: Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. RESULTS: Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. CONCLUSIONS: Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.

Clinicopathological significance of CHFR methylation in non-small cell lung cancer: a systematic review and meta-analysis.

Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a G2/M checkpoint and tumor-suppressor gene. Recent publications showed the correlation of CHFR promoter methylation with clinicopathological significance of non-small cell lung cancer (NSCLC), however, the results remain inconsistent. The aim of this study is to investigate the Clinicopathological significance of CHFR promoter methylation in NSCLC with a meta-analysis. A total of nine studies were included in the meta-analysis that 816 patients were involved. Our data indicated that the frequency of CHFR promoter methylation was higher in NSCLC than in normal lung tissue, Odd Ratios (OR) was 9.92 with 95% corresponding confidence interval (CI) 2.17-45.23, p = 0.003. Further subgroup analysis revealed that CHFR promoter was more frequently methylated in squamous cell carcinoma (SCC) than in adenocarcinoma (ADC), OR was 4.46 with 95% CI 1.65-12.05, p = 0.003, suggesting the mechanism of SCC pathogenesis is different from ADC. Notably, CHFR promoter methylation was correlated with smoking behavior in NSCLC. In conclusion, CHFR could be a biomarker for diagnosis of NSCLC, and a promising drug target for development of gene therapy in SCC. CHFR promoter methylation is potentially associated with poor overall survival, additional studies need to be carried out for confirmation in future.