Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China.
Turk J Gastroenterol. 2022 Dec;33(12):995-1003. doi: 10.5152/tjg.2022.211071.
Interleukin-17A is a proinflammatory cytokine that is produced by TH17 cells, and plays a dual role in tumor progression, infectious diseases, and autoimmune disorders. Interleukin-17A is induced during colorectal tumorigenesis and angiogenesis, although some studies have reported an anti-tumor effect as well. The aim of our study was to assess the prognostic role of interleukin-17A in colorectal cancer and determine the potential mechanisms.
The GEO database was searched using the keyword "colorectal cancer", and 10 datasets were identified that included interleukin-17A mRNA expression and survival data of several colorectal cancer patient cohorts. The patients were stratified into the interleukin-17Ahigh and interleukin-17Alow groups based on the median expression level.
Higher interleukin-17A mRNA levels were associated with better overall survival rates and the early tumor stage, indicating a protective role of interleukin-17A in colorectal cancer. Furthermore, interleukin-17A mRNA expression also correlated positively with that of TNFS11, CCR6, and CCL20, indicating that the anti-tumor effect of interleukin-17A is likely mediated by enhancing tumor antigen presentation by dendritic cells and recruiting the activated tumor-specific CD8+ cytotoxic T lymphocytes. The IL-23 and STAT3 mRNA levels were also significantly higher in the interleukin-17Ahigh group, which points to an upstream regulatory role of IL-23/STAT3 axis. Finally, the immune checkpoints PDCD1 (PD-1) and CD274 (PDL-1) were also positively correlated with interleukin-17A mRNA expression, indicating that interleukin-17A is a promising predictor of the immunotherapeutic outcome of PD-1/PDL-1 blockade in colorectal cancer.
Interleukin-17A mRNA is a protective factor in colorectal cancer and a promising biomarker for assessing the prognosis and immunotherapeutic response.
白细胞介素-17A 是一种促炎细胞因子，由 TH17 细胞产生，在肿瘤进展、传染病和自身免疫性疾病中发挥双重作用。白细胞介素-17A 在结直肠肿瘤发生和血管生成过程中被诱导，尽管一些研究也报道了其抗肿瘤作用。我们的研究目的是评估白细胞介素-17A 在结直肠癌中的预后作用，并确定潜在的机制。
使用关键字“结直肠癌”在 GEO 数据库中进行搜索，确定了包含几个结直肠癌患者队列的白细胞介素-17A mRNA 表达和生存数据的 10 个数据集。根据中位表达水平，将患者分为白细胞介素-17A 高和白细胞介素-17A 低两组。
较高的白细胞介素-17A mRNA 水平与较好的总生存率和早期肿瘤分期相关，表明白细胞介素-17A 在结直肠癌中具有保护作用。此外，白细胞介素-17A mRNA 表达也与 TNFS11、CCR6 和 CCL20 的表达呈正相关，表明白细胞介素-17A 的抗肿瘤作用可能是通过增强树突状细胞对肿瘤抗原的呈递和募集激活的肿瘤特异性 CD8+细胞毒性 T 淋巴细胞来介导的。白细胞介素-17A 高组的 IL-23 和 STAT3 mRNA 水平也显著升高，这表明 IL-23/STAT3 轴具有上游调节作用。最后，免疫检查点 PDCD1（PD-1）和 CD274（PDL-1）也与白细胞介素-17A mRNA 表达呈正相关，表明白细胞介素-17A 是评估结直肠癌 PD-1/PDL-1 阻断免疫治疗效果的有前途的预测因子。
白细胞介素-17A mRNA 是结直肠癌的保护因子，是评估预后和免疫治疗反应的有前途的生物标志物。
