Cancer Biomarkers - Volume 27, issue 4

Authors: Zhou, Wei | Chang, Aoshuang | Zhao, Houyu | Ye, Huiping | Li, Dairong | Zhuo, Xianlu

Article Type: Research Article

Abstract: BACKGROUND: Metastasis often leads to poor prognosis in nasopharyngeal carcinoma (NPC) patients. Evidence has indicated the important roles of microRNA (miRNA) in cancer metastasis. The aim of this study was to identify and verify the key miRNAs that might be involved in the development of NPC metastasis. METHODS: Microarray data were obtained and analyzed to screen the differentially expressed miRNAs (DEMs) between NPC tissues with metastasis and those without metastasis. The target genes of the DEMs were predicted and their functions were annotated. Then, candidate hub genes were screened out through protein-protein interaction analysis, and the …key miRNAs were identified. Afterwards, the expression levels of the key miRNAs were assessed by qRT-PCR based on an in vitro model. RESULTS: A total of 22 DEMs were screened out, and 616 target genes were predicted. Gene Ontology (GO) and pathway enrichment analysis showed that the target genes may be enriched in a diversity of GO terms and signaling pathways. Among them, eleven hub genes were identified, such as PTEN, KAT2B, CCND1, STAT3, and MAP3K5. Moreover, a five-miRNA profile (miR-106b, miR-17, miR-20b, miR-18a and miR-93) was identified and their expression levels were tested to be up-regulated in high-metastatic NPC cells relative to low-metastatic ones. CONCLUSION: The present study revealed that five miRNAs (miR-106b, miR-17, miR-20b, miR-18a and miR-93) and several hub genes such as PTEN, KAT2B, CCND1, STAT3, and MAP3K5, might play critical roles in the development of NPC metastasis. Future investigations are needed to confirm the results. Show more

Keywords: Nasopharyngeal carcinoma, metastasis, microRNA, microarray, qRT-PCR

DOI: 10.3233/CBM-190601

Citation: Cancer Biomarkers, vol. 27, no. 4, pp. 533-539, 2020

Authors: Fu, Tao | Ji, Xin | Bu, Zhaode | Zhang, Ji | Wu, Xiaojiang | Zong, Xianglong | Fan, Biao | Jia, Ziyu | Ji, Jiafu

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer is the third leading cause of cancer-related deaths worldwide. OBJECTIVE: The present study aims to identify key long non-coding RNAs (lncRNAs) and their potential roles in the pathogenesis of gastric adenocarcinoma. METHODS: The lncRNA and mRNA expression profile between gastric adenocarcinoma and adjacent non-tumor tissues were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between gastric adenocarcinoma and adjacent non-tumor tissues were identified after bioinformatics analysis. DElncRNA-DEmRNA co-expression network and DElncRNA-nearby DEmRNA interaction network were constructed, respectively. Functional annotation for DEmRNAs interacted with DElncRNAs …was performed. Receiver operating characteristic (ROC) analysis of selected DElncRNAs was conducted. RESULTS: Based on TCGA, the mRNA and lncRNA expression profiles of 375 gastric adenocarcinoma and 32 adjacent non-tumor tissues were downloaded. A total of 1502 DEmRNAs and 928 DElncRNAs between gastric adenocarcinoma and adjacent non-tumor tissues were identified. HOXC-AS3 might involve with gastric adenocarcinoma by regulating a set of HOX genes (HOXC8, HOXC9, HOXC10, HOXC11, HOXC12 and HOXC13) with cis-effect. AC115619.1-APOA4/APOB and AP006216.2-APOA1/APOA4 integrations might play roles in gastric adenocarcinoma through regulating pathways of Fat digestion and absorption and Vitamin digestion and absorption. Six lncRNAs including (HOTAIR, C20orf166-AS1, PGM5-AS1, HOXC-AS3, HOXC-AS2 and AC012531.1) have excellent diagnostic value for gastric adenocarcinoma. CONCLUSIONS: This study identifies key lncRNAs in gastric adenocarcinoma which provides clues for exploring the pathogenesis and developing potential biomarkers for gastric adenocarcinoma. Show more

Keywords: Gastric adenocarcinoma, The Cancer Genome Atlas (TCGA), long non-coding RNAs (lncRNAs), mRNA, biomarker

DOI: 10.3233/CBM-192389

Citation: Cancer Biomarkers, vol. 27, no. 4, pp. 541-553, 2020

Authors: Pirim, Dilek

Article Type: Research Article

Abstract: BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths and mining the molecular factors underlying CRC pathogenesis is imperative for alleviating the disease burden. OBJECTIVE: To highlight key molecular pathways, prioritize hub genes and their regulators related to CRC. METHODS: Data sets of TCGA-COAD and GTEx were used to identify differentially expressed genes (DEGs) and their functional enrichments in pathways and biological processes were analyzed using bioinformatics tools. Protein-protein interaction network was constructed and hub genes were identified using Cytoscape. Ingenuity Pathway Analysis was used to analyze the relations …of the hub genes with diseases and canonical pathways. Key regulators targeting the hub genes such as TFs, miRNAs and their interactions were identified using in silico tools. RESULTS: AURKA , CDK1 , MYC , CDH1 , CCNB1 , CDC20 , UBE2C , PLK1 , KIF11 , and CCNA2 were prioritized as hub genes based on their topological properties. Enrichment analyses emphasized the roles of DEGs and hub genes in the cell cycle process. Interactions of the hub genes with TFs and miRNAs suggested TP53, EZH2 and KLF4 as being promising candidate biomarkers for CRC. CONCLUSIONS: Our results provide in silico evidence for candidate biomolecules that may have strong biomarker potential for CRC-related translational strategies. Show more

Keywords: Colorectal cancer, microRNA, transcription factors, in silico tools, bioinformatics, Ingenuity Pathway Analysis

DOI: 10.3233/CBM-191263

Citation: Cancer Biomarkers, vol. 27, no. 4, pp. 555-568, 2020