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Background: Risk of colorectal cancer (CRC) is defined by genetic predisposition and environmental factors that often co-occur and interact, resulting in diversiform biological reactions. The present study attempted to investigate transcriptome alteration and adaptation associated with CRC progression. Methods: The study consisted of patients who presented at Memorial Sloan-Kettering Cancer Center, Guangzhou, China with a colonic neoplasm in 1992-2004. Microarray GSE41258 of the study was acquired from Gene Expression Omnibus and 253 included microarrays were categorized by groups of normal colon, early primary tumor, lymph node metastases primary tumor, advanced primary tumor and distant metastases. Short Time-series Expression Miner (STEM) was applied to discover tumor grade-dependent gene expression patterns. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to explore functional enrichment of differential expression genes (DEGs). Results: Overall, 2870 significant DEGs were screened out on all groups. Six significant grade-dependent gene expression patterns were statistically significant. DEGs in all significant patterns were mainly assembled in GO terms of metastases and deterioration of tumor, epithelial proteins and cytokines, and protein binding and bridging. DEGs in profile 0 down-regulated with higher tumor grade, prominently enriched in KEGG pathways of metabolism. Conclusion: Besides many well-known colorectal cancer-related pathways, DEGs of profiles especially those down-regulated with CRC progression, clustered in various metabolic pathways including starch and sucrose metabolism, fatty acid metabolism, nitrogen metabolism, as well as xenobiotics biotransformation that link to tumorigenesis, demonstrating the impairment of physiological metabolic pathways in the context of tumor progression. These results gave a high potential for therapeutic strategies.

The goal of the present study was to identify different transcriptome expression profiles involved in the pathogenesis of deep vein thrombosis (DVT), and to illustrate the diagnostic and therapeutic potential of circular RNAs (circRNAs) and mRNAs in DVT progression. A Sprague-Dawley rat model of DVT was successfully established through the stenosis method and samples were sequenced at four time points (1, 6 and 12 h, and 3 days after ligation) to observe the dynamic changes in circRNAs and mRNAs during DVT progression. RNA sequencing was used to analyze the circRNA and mRNA expression profiles, and associated functions and pathways, in the blood of DVT rats at the four time points. In addition, Short Time Series Expression Miner (STEM) analysis was performed to explore temporal gene expression. Differential expression of 1,680, 4,018, 3,724, and 3,036 circRNAs, and 400, 1,176, 373, and 573 mRNAs was observed in the 1, 6 and 12 h, and 3-day groups, respectively, compared with the sham group (fold change >2.0 or <-2.0, P<0.05). Functional enrichment analysis indicated that differentially expressed mRNAs were associated with the following terms: Immune response, cell activation, blood stasis facilitated organelle, extracellular membrane-bounded organelle, and blood microparticle, oxygen transporter activity. STEM analysis indicated that the expression of 366 circRNAs in circRNA profile 45 and 270 mRNAs in mRNA profile 45 was consistent with thrombus progression. Enrichment analysis was performed on mRNA profile 45. The main Gene Ontology annotations were chromosome segregation, mitotic sister chromatid segregation, cell cycle process, and ligand-dependent nuclear receptor transcription coactivator activity. Pathway enrichment analysis identified the platelet-associated pathway, immune-associated pathway, and inflammation-relation pathway. According to the enriched platelet-associated pathways, four mRNAs and ten candidate circRNAs were selected for reverse transcription-quantitative PCR verification. The expression of nine of the ten circRNAs and all four mRNAs was consistent with the sequencing results. In summary, differentially expressed circRNAs and mRNAs are dynamically involved in DVT development. Dysregulated transcriptome profiles and the corresponding functions and pathways may provide mechanistic insights into DVT diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Risk of colorectal cancer (CRC) is defined by genetic predisposition and environmental factors that often co-occur and interact, resulting in diversiform biological reactions. The present study attempted to investigate transcriptome alteration and adaptation associated with CRC progression., Methods: The study consisted of patients who presented at Memorial Sloan-Kettering Cancer Center, Guangzhou, China with a colonic neoplasm in 1992-2004. Microarray GSE41258 of the study was acquired from Gene Expression Omnibus and 253 included microarrays were categorized by groups of normal colon, early primary tumor, lymph node metastases primary tumor, advanced primary tumor and distant metastases. Short Time-series Expression Miner (STEM) was applied to discover tumor grade-dependent gene expression patterns. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to explore functional enrichment of differential expression genes (DEGs)., Results: Overall, 2870 significant DEGs were screened out on all groups. Six significant grade-dependent gene expression patterns were statistically significant. DEGs in all significant patterns were mainly assembled in GO terms of metastases and deterioration of tumor, epithelial proteins and cytokines, and protein binding and bridging. DEGs in profile 0 down-regulated with higher tumor grade, prominently enriched in KEGG pathways of metabolism., Conclusion: Besides many well-known colorectal cancer-related pathways, DEGs of profiles especially those down-regulated with CRC progression, clustered in various metabolic pathways including starch and sucrose metabolism, fatty acid metabolism, nitrogen metabolism, as well as xenobiotics biotransformation that link to tumorigenesis, demonstrating the impairment of physiological metabolic pathways in the context of tumor progression. These results gave a high potential for therapeutic strategies., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright© Iranian Public Health Association & Tehran University of Medical Sciences.)