Identification, Validation, and Functional Annotations of Genome-Wide Profile Variation between Melanocytic Nevus and Malignant Melanoma
BIOMED RESEARCH INTERNATIONAL
Authors: Han, Wei; Xu, Wen-Hao; Wang, Jian-Xiong; Hou, Jia-Min; Zhang, Hai-Liang; Zhao, Xiao-Yu; Shen, Guo-Liang
Abstract
Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades. This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation. A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma. In addition, survival curves indicated that six hub genes, includingFABP5,IVL,KRT6A,KRT15,KRT16, andTIMP2, were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma. Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort. It suggested that significantly elevatedFABP5,IVL,KRT6A,KRT15,KRT16, andTIMP2proteins expressed in the CM than in the nevus tissues. Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include theP53pathway,K-rassignaling, estrogen response late, and estrogen response early. In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles ofFABP5,IVL,KRT6A,KRT15,KRT16, andTIMP2provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma.
Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma
ONCOTARGET
Authors: Xiao, Jian; Lu, Xiaoxiao; Chen, Xi; Zou, Yong; Liu, Aibin; Li, Wei; He, Bixiu; He, Shuya; Chen, Qiong
Abstract
Lung adenocarcinoma (LADC) and squamous cell carcinoma (LSCC) are the most common non-small cell lung cancer histological phenotypes. Accurate diagnosis distinguishing between these two lung cancer types has clinical significance. For this study, we analyzed four Gene Expression Omnibus (GEO) datasets (GSE28571, GSE37745, GSE43580, and GSE50081). We then imported the datasets into the Gene-Cloud of Biotechnology Information online platform to identify genes differentially expressed in LADC and LSCC. We identified DSG3 (desmoglein 3), KRT5 (keratin 5), KRT6A (keratin 6A), KRT6B (keratin 6B), NKX2-1 (NK2 homeobox 1), SFTA2 (surfactant associated 2), SFTA3 (surfactant associated 3), and TMC5 (transmembrane channel-like 5) as potential biomarkers for distinguishing between LADC and LSCC. Receiver operating characteristic curve analysis suggested that KRT5 had the highest diagnostic value for discriminating between these two cancer types. Using the PrognoScan online survival analysis tool and the Kaplan-Meier Plotter, we found that high KRT6A or KRT6B levels, or low NKX2-1, SFTA3, or TMC5 levels correlated with unfavorable prognoses in LADC patients. Further studies will be needed to verify our findings in additional patient samples, and to elucidate the mechanisms of action of these potential biomarkers in non-small cell lung cancer.