Liu Fuguo, Ji Fengzhi, Ji Yuling, Jiang Yueping, Sun Xueguo, Lu Yanyan, Zhang Lingyun, Han Yue, Liu Xishuang
Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong 266003, P.R. China.
Statistics Division, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong 266003, P.R. China.
Int J Mol Med. 2015 Oct;36(4):923-30. doi: 10.3892/ijmm.2015.2298. Epub 2015 Jul 30.
The present study aimed to investigate the molecular targets for colorectal cancer (CRC). Differentially expressed genes (DEGs) were screened between CRC and matched adjacent noncancerous samples. GENETIC_ASSOIATION_DB_DISEASE analysis was performed to identify CRC genes from the identified DEGs using the Database for Annotation, Visualization and Integrated Discovery, followed by Gene Οntology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis for the CRC genes. A protein‑protein interaction (PPI) network was constructed for the CRC genes, followed by determination and analysis of the hub genes, in terms of the protein domains and spatial structure. In total, 35 CRC genes were determined, including 19 upregulated and 16 downregulated genes. Downregulated N‑acetyltransferase (NAT)1 and NAT2 were enriched in the caffeine metabolism pathway. The downregulated and upregulated genes were enriched in a number of GO terms and pathways, respectively. Cyclin D1 (CCND1) and proliferating cell nuclear antigen (PCNA) were identified as the hub genes in the PPI network. The C‑terminal and N‑terminal domains were similar in PCNA, but different in CCND1. The results suggested PCNA, CCND1, NAT1 and NAT2 for use as biomarkers to enable early diagnosis and monitoring of CRC. These results form a basis for developing therapies, which target the unique protein domains of PCNA and CCND1.
本研究旨在探究结直肠癌(CRC)的分子靶点。在CRC与匹配的相邻非癌样本之间筛选差异表达基因(DEG)。使用注释、可视化与整合发现数据库对鉴定出的DEG进行GENETIC_ASSOIATION_DB_DISEASE分析,以鉴定CRC基因,随后对CRC基因进行基因本体(GO)分析和京都基因与基因组百科全书分析。为CRC基因构建蛋白质-蛋白质相互作用(PPI)网络,随后根据蛋白质结构域和空间结构确定并分析枢纽基因。共确定了35个CRC基因,包括19个上调基因和16个下调基因。下调的N-乙酰转移酶(NAT)1和NAT2在咖啡因代谢途径中富集。下调基因和上调基因分别在多个GO术语和途径中富集。细胞周期蛋白D1(CCND1)和增殖细胞核抗原(PCNA)被鉴定为PPI网络中的枢纽基因。PCNA的C末端和N末端结构域相似,但CCND1不同。结果表明PCNA、CCND1、NAT1和NAT2可作为生物标志物用于CRC的早期诊断和监测。这些结果为开发针对PCNA和CCND1独特蛋白质结构域的治疗方法奠定了基础。