JAK/STAT pathway has been well confirmed in the development of colorectal cancer (CRC), however, the exact mechanism is unclear. Therefore, we aimed to identify key genes involved in JAK/STAT pathway in CRC, as well as the potential mechanism. RT² profiler PCR arrays were performed to identify key genes of the JAK/STAT pathway. GO, KEGG pathway and PPI analyses were performed to screen the main functions of differentially expressed genes (DEGs). Moreover, the expression of DEGs was detected by GEPIA based on TCGA database and verified by qPCR and/or Western blot. Subsequently, the association between the two DEGs (CXCL9 and IL6ST) and clinicopathological features were determined by immunohistochemistry, and survival analysis was also conducted. Finally, the effects of IL6ST overexpression on STAT3 activation and HT29 cell functions were analyzed. A total of 14 DEGs were identified. Among the DEGs, GHR, NR3C1, IL6ST and A2M were confirmed to be statistically decreased, while CXCL9 was significantly increased in the CRC tissues. Furthermore, CXCL9 was significantly associated with differentiation, lymph node metastasis, distant metastasis and invasion, while IL6ST was related with tumor size, differentiation, stage and invasion. Patients with high expression of IL6ST presented significantly lower lifetime, however, CXCL9 showed the opposite results without significance. Additionally, we found that overexpression of IL6ST statistically elevated p-STAT3 level, cell viability, adhesion rate and migration, and decreased apoptosis, but had no effects on cell cycle. Our results suggest that IL6ST is a critical key gene involved in JAK/STAT signaling pathway in CRC.

JAK / STAT通路已在结直肠癌（CRC）的发展中得到了很好的证实，但是，确切的机制尚不清楚。因此，我们旨在鉴定参与CRC的JAK / STAT通路的关键基因及其潜在机制。进行了RT²分析仪PCR阵列鉴定JAK / STAT途径的关键基因。进行GO，KEGG途径和PPI分析以筛选差异表达基因（DEG）的主要功能。此外，DEGs的表达通过基于TCGA数据库的GEPIA检测并通过qPCR和/或Western印迹验证。随后，通过免疫组织化学确定了两个DEG（CXCL9和IL6ST）与临床病理特征之间的关联，并进行了生存分析。最后，分析了IL6ST过表达对STAT3激活和HT29细胞功能的影响。总共鉴定出14个DEG。在DEG中，证实CRC组织中GHR，NR3C1，IL6ST和A2M显着降低，而CXCL9显着升高。此外，CXCL9与分化，淋巴结转移，远处转移和侵袭显着相关，而IL6ST与肿瘤大小，分化，分期和侵袭有关。高表达IL6ST的患者的生存期显着降低，但是CXCL9却显示了相反的结果，但无统计学意义。此外，我们发现IL6ST的过表达在统计学上提高了p-STAT3水平，细胞活力，粘附率和迁移，并减少了细胞凋亡，但对细胞周期没有影响。我们的结果表明，IL6ST是参与CRC的JAK / STAT信号通路的关键关键基因。