Molecular subtypes based on DNA methylation predict prognosis in lung squamous cell carcinoma.

BACKGROUND: Due to tumor heterogeneity, the diagnosis, treatment, and prognosis of patients with lung squamous cell carcinoma (LUSC) are difficult. DNA methylation is an important regulator of gene expression, which may help the diagnosis and therapy of patients with LUSC. METHODS: In this study, we collected the clinical information of LUSC patients in the Cancer Genome Atlas (TCGA) database and the relevant methylated sequences of the University of California Santa Cruz (UCSC) database to construct methylated subtypes and performed prognostic analysis. RESULTS: Nine hundred sixty-five potential independent prognosis methylation sites were finally identified and the genes were identified. Based on consensus clustering analysis, seven subtypes were identified by using 965 CpG sites and corresponding survival curves were plotted. The prognostic analysis model was constructed according to the methylation sites' information of the subtype with the best prognosis. Internal and external verifications were used to evaluate the prediction model. CONCLUSIONS: Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients.

Identification of potential crucial genes associated with the pathogenesis and prognosis of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a type of malignant tumor with the highest mortality rate among all neoplasms worldwide, and its exact pathogenesis is still poorly understood. Timely diagnosis and treatment are of great importance in order to decrease the mortality rate of PAAD. Therefore, identifying new biomarkers for diagnosis and prognosis is essential to enable early detection of PAAD and to improve the overall survival (OS) rate. In order to screen and integrate differentially expressed genes (DEGs) between PAAD and normal tissues, a total of seven datasets were downloaded from the Gene Expression Omnibus database and the 'limma' and 'robustrankggreg' packages in R software were used. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery website, and the protein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. A gene prognostic signature was constructed using the Cox regression model. A total of 10 genes (CDK1, CCNB1, CDC20, ASPM, UBE2C, TPX2, TOP2A, NUSAP1, KIF20A and DLGAP5) that may be associated with pancreatic adenocarcinoma were identified. According to the differentially expressed genes in The Cancer Genome Atlas, the present study set up four prognostic signatures (matrix metalloproteinase 12, sodium voltage-gated channel α subunit 11, tetraspanin 1 and SH3 domain and tetratricopeptide repeats-containing 2), which effectively predicted OS. The hub genes that were highly associated with the occurrence, development and prognosis of PAAD were identified, which may be helpful to further understand the molecular basis of pancreatic cancer and guide the synthesis of drugs for PPAD.

Identification of hub genes correlated with the pathogenesis and prognosis in Pancreatic adenocarcinoma on bioinformatics methods.

BACKGROUND: Pancreatic adenocarcinoma (PC), is a type of digestive tract cancer with the highest mortality all over the word, and its exact pathogenesis is not clear. Therefore, it is of great significance to search for genes related to PC and elucidate its molecular mechanism. METHODS: We integrated and analyzed 8 microarray datasets from the Gene Expression Comprehensive Database (GEO) and PC patient information from the Cancer Genome Atlas (TCGA) database to identified differentially expressed genes (DEGs) based on standardized annotation information. The overlapped DEGs both in the GEO and TCGA datasets were identified as key genes. Kaplan-Meier comprehensive expression scoring method was conducted to determine whether the key genes are related to the survival rate of PC. The expression of those key genes was analyzed by GEPIA and UALCAN. Lastly, Cox regression model was used to construct a gene prognosis signature. RESULTS: The TSPAN1 gene was identified that might be highly related to the pathogenesis of PC. Further analysis showed high expression of TSPAN1 was closely related to the stage 2, moderately differentiated (intermediate grade), and poorly differentiated (high grade) of PC. Finally, we build a four-gene prognosis signature (AIM2, B3GNT3, MATK and BEND4), which can be applied to predict overall survival (OS) effectively. CONCLUSIONS: We revealed promising genes that may participate in the pathophysiology of PC, and found available biomarkers for PC prognosis prediction, which were significant for researchers to further understand the molecular basis of PC and direct the synthesis medicine of PC.