Analysis of potential genes and pathways associated with the colorectal normal mucosa-adenoma-carcinoma sequence

Abstract

This study aimed to identify differentially expressed genes (DEGs) related to the colorectal normal mucosa-adenoma-carcinoma sequence using bioinformatics analysis. Raw data files were downloaded from Gene Expression Omnibus (GEO) and underwent quality assessment and preprocessing. DEGs were analyzed by the limma package in R software (R version 3.3.2). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with the DAVID online tool. In a comparison of colorectal adenoma (n = 20) and colorectal cancer (CRC) stage I (n = 31), II (n = 38), III (n = 45), and IV (n = 62) with normal colorectal mucosa (n = 19), we identified 336 common DEGs. Among them, seven DEGs were associated with patient prognosis. Five (HEPACAM2, ITLN1, LGALS2, MUC12, and NXPE1) of the seven genes presented a sequentially descending trend in expression with tumor progression. In contrast, TIMP1 showed a sequentially ascending trend. GCG was constantly downregulated compared with the gene expression level in normal mucosa. The significantly enriched GO terms included extracellular region, extracellular space, protein binding, and carbohydrate binding. The KEGG categories included HIF-1 signaling pathway, insulin secretion, and glucagon signaling pathway. We discovered seven DEGs in the normal colorectal mucosa-adenoma-carcinoma sequence that was associated with CRC patient prognosis. Monitoring changes in these gene expression levels may be a strategy to assess disease progression, evaluate treatment efficacy, and predict prognosis.

Keywords: Colorectal normal mucosa-adenoma-carcinoma sequence; differentially expressed genes; functional analysis; microarray analysis; prognosis.

Figure 1

Flowchart of selecting eligible datasets.

Figure 2

Venn diagram for (A) the 336 common DEGs with threshold of |log₂ FC| >1 and an adjusted P‐value <0.05 and for (B) the six common DEGs with threshold of |log₂ FC| >4 and an adjusted P‐value <0.05 extracted from normal mucosa–adenoma, normal mucosa–CRC stage I, normal mucosa–CRC stage II, normal mucosa–CRC stage III, and normal mucosa–CRC stage IV. FC, fold change.

Figure 3

Survival curve of (A) HEPACAM2, (B) ITLN1, (C) LGALS2, (D) MUC12, (E) NXPE1, (F) TIMP1, and (G) GCG.