Abstract
Colorectal cancer (CRC) is the second most deadly cancer in the whole world, with the underlying mechanisms largely indistinct. Therefore, we aimed to identify significant pathways and genes involved in the initiation, formation and poor prognosis of CRC using bioinformatics methods. In this study, we compared gene expression profiles of CRC cases with those from normal colorectal tissues from three chip datasets (GSE33113, GSE23878 and GSE41328) to identify 105 differentially expressed genes (DEGs) that were common to the three datasets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the highest proportion of up-regulated DEGs was involved in extracellular region and cytokine-cytokine receptor interaction pathways. Integral components of membrane and bile secretion pathways were identified as containing down-regulated DEGs. 13 hub DEGs were chosen and their expression were further validated by GEPIA. Only four DEGs (ADH1C, CLCA4, CXCL8 and GUCA2A) were associated with a significantly lower overall survival after the prognosis analysis. Lower ADH1C protein level and higher CXCL8 protein level were verified by immunohistochemical staining and western blot in clinical CRC and normal colorectal tissues. In conclusion, our study indicated that the extracellular tumor microenvironment and bile metabolism pathways play critical roles in the formation and progression of CRC. Furthermore, we confirmed ADH1C being down-regulated in CRC and reported ADH1C as a prognostic predictor for the first time.
Highlights
Colorectal cancer (CRC) causes approximately 10% of cancer-related deaths each year and is the second most common lethal cancers globally (Dekker et al, 2019; Sung et al, 2021)
A total of 105 differentially expressed genes (DEGs) were identified as common to the three databases. These included 22 up-regulated DEGs and 83 downregulated DEGs in the CRC tissues when compared with the normal colorectal tissues (Table 1 and Figure 1)
The gene ontology (GO) analysis showed that the highest proportion of up-regulated DEGs were involved in 1) collagen catabolic process, cell-cell signaling, extracellular matrix disassembly, negative regulation of protein kinase activity, and positive regulation of protein oligomerization, found in the biological process (BP)
Summary
Colorectal cancer (CRC) causes approximately 10% of cancer-related deaths each year and is the second most common lethal cancers globally (Dekker et al, 2019; Sung et al, 2021). High-throughput sequencing technology is powerful for screening differentially expressed genes (DEGs) in biological samples (Vogelstein et al, 2013) This has led to an increase in the number of gene expression profiles researches and a huge amount of data have been accumulated in public databases, of which bioinformatic analysis is necessary to obtain valuable insights into disease mechanisms. This is the case with CRC (Isella et al, 2015) and a lot of data on CRC-related DEGs have been accumulating in the database. Bioinformatics studies on CRC, based on public databases (Guo et al, 2017), have shown that using these methods will help to explain the formation of the disease and reveal the underlying molecular mechanisms
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