Wu Qi-Qiao, Wang Xing-Yue, Wu Wei-Xun, Chen Yi-Xing, Wang Jian, Zhang Xian, Qian Yang, Du Shi-Suo, Sun Jing, Zeng Zhao-Chong
Department of Radiation Oncology, Fudan University Zhongshan Hospital, Xiamen Branch, Jinhu Road 668, Xiamen, 361006, China.
Department of Nutrition, Fudan University Zhongshan Hospital, Xiamen Branch, Jinhu Road 668, Xiamen, 361006, China.
Cancer Treat Res Commun. 2023;35:100694. doi: 10.1016/j.ctarc.2023.100694. Epub 2023 Feb 23.
Colorectal cancer (CRC) is one of the most common cancers worldwide. As the molecular mechanism for liver metastasis of CRC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing potential molecular mechanism of colorectal cancer progression. This study aimed to identify potential biomarkers and survival analysis of hub genes for CRC treatment.
The differentially expressed genes (DEGs) between colorectal cancer liver metastasis and primary tumor were screened using microarray data from two datasets GSE179979, GSE144259 obtained from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS), progression free interval (PFI) and disease specific survival (DSS) analysis of hub genes was performed by using TCGA database. The correlations between hub genes and clinical values were validated through CRN and immunohistochemistry (IHC) stain.
A total of 64 DEGs were obtained, KEGG pathway analysis showed that the significant pathways included PPAR signaling pathway, Complement and coagulation cascades. Four hub genes (ITIH2, ALB, CPB2, HGFAC) and two biomarkers (CPB2, HGFAC) with significantly prognostic values were verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort.
CPB2 and HGFAC may serve as new biomarkers in diagnosing liver metastasis of CRC or potential drug target.
结直肠癌（CRC）是全球最常见的癌症之一。由于CRC肝转移的分子机制尚未完全发现，确定该疾病的枢纽基因和通路对于揭示结直肠癌进展的潜在分子机制具有重要意义。本研究旨在确定CRC治疗的潜在生物标志物并对枢纽基因进行生存分析。
使用从基因表达综合数据库（GEO）获得的两个数据集GSE179979、GSE144259的微阵列数据，筛选结直肠癌肝转移与原发性肿瘤之间的差异表达基因（DEGs）。使用DAVID数据库对DEGs进行基因本体（GO）和KEGG通路富集分析，使用Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络，并使用MCODE进行模块分析。然后，使用TCGA数据库对枢纽基因进行总生存（OS）、无进展生存期（PFI）和疾病特异性生存（DSS）分析。通过CRN和免疫组织化学（IHC）染色验证枢纽基因与临床值之间的相关性。
共获得64个DEGs，KEGG通路分析表明，显著通路包括PPAR信号通路、补体和凝血级联反应。通过基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）队列验证了四个具有显著预后价值的枢纽基因（ITIH2、ALB、CPB2、HGFAC）和两个生物标志物（CPB2、HGFAC）。
CPB2和HGFAC可能作为诊断CRC肝转移的新生物标志物或潜在的药物靶点。
