Niu Mengke, Yi Ming, Dong Bing, Luo Suxia, Wu Kongming
Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ann Transl Med. 2020 Aug;8(15):951. doi: 10.21037/atm-20-4428.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women globally. Investigating genetic ground differences between normal and CRC tissues would be significant for identifying some key oncogenic pathways and developing anti-cancer agents.
Weighted gene co-expression network analysis (WGCNA) method was used to screen out core pathways related to the clinical traits of CRC patients. Then, multiple databases were utilized to further verify the hub genes obtained from data mining. Finally, to explore the role of hub genes in CRC, cell counting and EdU assays were performed.
The results of the WGCNA analysis showed that a module (turquoise module) was highly related with CRC differentiation grade (R =0.53, P<0.0001). Enrichment analysis indicated that genes of the turquoise module were remarkably enriched in multiple inflammatory processes and pathways. Among all hub genes of the turquoise module, the mRNA levels of and were significantly higher in CRC than in normal colon tissues. expression was highly positively correlated with the level of . The results of the cell counting, EdU, CCK-8, and CFSE staining assays showed that interfering with STAT1 and CCL5 could inhibit the proliferation of CRC cells.
Our study indicated that the STAT1-CCL5 axis is an important modulator in the development of CRC through promoting cell proliferation. Moreover, the levels of STAT1 and CCL5 might be valuable biomarkers for CRC screening.
结直肠癌（CRC）是全球男性和女性中第三大最常被诊断出的癌症。研究正常组织与CRC组织之间的基因差异对于识别一些关键致癌途径和开发抗癌药物具有重要意义。
使用加权基因共表达网络分析（WGCNA）方法筛选出与CRC患者临床特征相关的核心途径。然后，利用多个数据库进一步验证从数据挖掘中获得的枢纽基因。最后，为了探究枢纽基因在CRC中的作用，进行了细胞计数和EdU检测。
WGCNA分析结果显示，一个模块（绿松石模块）与CRC分化程度高度相关（R = 0.53，P < 0.0001）。富集分析表明，绿松石模块的基因在多个炎症过程和途径中显著富集。在绿松石模块的所有枢纽基因中，CRC中 和 的mRNA水平显著高于正常结肠组织。 的表达与 的水平高度正相关。细胞计数、EdU、CCK - 8和CFSE染色检测结果表明，干扰STAT1和CCL5可抑制CRC细胞的增殖。
我们的研究表明，STAT1 - CCL5轴通过促进细胞增殖是CRC发生发展中的重要调节因子。此外，STAT1和CCL5的水平可能是CRC筛查中有价值的生物标志物。
