Shen Qiu, Lu Chao, Yang Hua, Ge Ming-Xia, Xia Wang-Xiao, Kong Qing-Peng, Li Gong-Hua, Gu Yan-Hong
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
State Key Laboratory of Genetic Resources and Evolution/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
PeerJ. 2020 Feb 11;8:e8421. doi: 10.7717/peerj.8421. eCollection 2020.
Colon adenocarcinoma (COAD) represents a major public health issue due to its high incidence and mortality. As different histological subtypes of COAD are related to various survival outcomes and different therapies, finding specific targets and treatments for different subtypes is one of the major demands of individual disease therapy. Interestingly, as these different subtypes show distinct metabolic profiles, it may be possible to find specific targets related to histological typing by targeting COAD metabolism. In this study, the differential expression patterns of metabolism-related genes between COAD ( = 289) and adjacent normal tissue ( = 41) were analyzed by one-way ANOVA. We then used weighted gene co-expression network analysis (WGCNA) to further identify metabolism-related gene connections. To determine the critical genes related to COAD metabolism, we obtained 2,114 significantly differentially expressed genes (DEGs) and 12 modules. Among them, we found the hub module to be significantly associated with histological typing, including non-mucin-producing colon adenocarcinoma and mucin-producing colon adenocarcinoma. Combining survival analysis, we identified glycerophosphodiester phosphodiesterase 1 (GDE1) as the most significant gene associated with histological typing and prognosis. This gene displayed significantly lower expression in COAD compared with normal tissues and was significantly correlated with the prognosis of non-mucin-producing colon adenocarcinoma ( = 0.0017). Taken together, our study showed that GDE1 exhibits considerable potential as a novel therapeutic target for non-mucin-producing colon adenocarcinoma.
结肠腺癌（COAD）因其高发病率和死亡率而成为一个重大的公共卫生问题。由于COAD的不同组织学亚型与各种生存结果和不同治疗方法相关，寻找不同亚型的特定靶点和治疗方法是个体化疾病治疗的主要需求之一。有趣的是，由于这些不同亚型表现出不同的代谢特征，通过靶向COAD代谢来寻找与组织学分型相关的特定靶点可能是可行的。在本研究中，通过单因素方差分析分析了COAD（n = 289）和相邻正常组织（n = 41）之间代谢相关基因的差异表达模式。然后我们使用加权基因共表达网络分析（WGCNA）来进一步识别代谢相关基因连接。为了确定与COAD代谢相关的关键基因，我们获得了2114个显著差异表达基因（DEG）和12个模块。其中，我们发现枢纽模块与组织学分型显著相关，包括非黏液产生型结肠腺癌和黏液产生型结肠腺癌。结合生存分析，我们确定甘油磷酸二酯磷酸二酯酶1（GDE1）是与组织学分型和预后最相关的基因。与正常组织相比，该基因在COAD中的表达显著降低，并且与非黏液产生型结肠腺癌的预后显著相关（P = 0.0017）。综上所述，我们的研究表明GDE1作为非黏液产生型结肠腺癌的新型治疗靶点具有相当大的潜力。
