与免疫微环境相关的mA调控因子的表达在胰腺导管腺癌的预后中起重要作用。
The expression of mA regulators correlated with the immune microenvironment plays an important role in the prognosis of pancreatic ductal adenocarcinoma.
作者信息
Yao Yutong, Luo Le, Xiang Guangming, Xiong Junjie, Ke Nengwen, Tan Chunlu, Chen Yonghua, Liu Xubao
机构信息
Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Hepatobiliary and Pancreatic Surgery Center, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
出版信息
Gland Surg. 2022 Jan;11(1):147-165. doi: 10.21037/gs-21-859.
BACKGROUND
The relationship between N6-methyladenosine (mA) RNA methylation regulators and the tumor immune microenvironment has been extensively studied. Nevertheless, the potential function of mA regulators in the tumor immune landscape of pancreatic ductal adenocarcinoma (PDAC) remains to be fully elucidated.
METHODS
Here, we systematically evaluated the expression of 19 mA regulators in PDAC patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Utilizing consensus clustering, the PDAC patients were segmented into two subgroups according to the expression of 19 mA regulators. A prognostic risk signature of 5 mA methylation regulators (, , , , and ) was then built, and the PDAC patients were divided into high-risk and low-risk groups. Subsequently, differences in independent prognostic parameters, risk score distribution, survival, and cluster analysis between high-risk and low-risk groups were analyzed.
RESULTS
We found two subgroups with dramatically different immune landscapes and prognoses. Subsequently, differences in independent prognostic parameters, risk score distribution, survival, and cluster analysis between the high-risk and low-risk groups were found. Moreover, these gene signatures displayed good discriminative performances in the GEO datasets. We also found that the risk score was positively correlated with the tumor mutation burden (TMB), and the TMB value was higher in the high-risk scoring group. The low-risk scoring group was linked by a stronger response to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy and clinical advantages in the immunotherapeutic advanced urothelial cancer (IMvigor210) cohort. Ultimately, we found that these 5 mA regulators had a fatal regulatory role on the tumor immune microenvironment in PDAC patients.
CONCLUSIONS
The construction signature based on the mA regulators may be crucial regulators of the tumor immune microenvironment in PDAC, providing a new approach to improving the immunotherapy strategy for PDAC patients.
背景
N6-甲基腺苷（m⁶A）RNA甲基化调节剂与肿瘤免疫微环境之间的关系已得到广泛研究。然而，m⁶A调节剂在胰腺导管腺癌（PDAC）肿瘤免疫格局中的潜在功能仍有待充分阐明。
方法
在此，我们系统评估了来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的PDAC患者中19种m⁶A调节剂的表达情况。利用一致性聚类，根据19种m⁶A调节剂的表达将PDAC患者分为两个亚组。然后构建了由5种m⁶A甲基化调节剂（ 、 、 、 和 ）组成的预后风险特征，并将PDAC患者分为高风险组和低风险组。随后，分析了高风险组和低风险组在独立预后参数、风险评分分布、生存率及聚类分析方面的差异。
结果
我们发现了两个具有显著不同免疫格局和预后的亚组。随后，发现了高风险组和低风险组在独立预后参数、风险评分分布、生存率及聚类分析方面的差异。此外，这些基因特征在GEO数据集中表现出良好的判别性能。我们还发现风险评分与肿瘤突变负荷（TMB）呈正相关，且高风险评分组的TMB值更高。低风险评分组与抗程序性细胞死亡配体1（抗PD-L1）免疫治疗的更强反应以及免疫治疗晚期尿路上皮癌（IMvigor210）队列中的临床优势相关。最终，我们发现这5种m⁶A调节剂对PDAC患者的肿瘤免疫微环境具有关键调节作用。
结论
基于m⁶A调节剂构建的特征可能是PDAC肿瘤免疫微环境的关键调节因子，为改善PDAC患者的免疫治疗策略提供了新方法。
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