Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2022 Sep 23;13:1000321. doi: 10.3389/fimmu.2022.1000321. eCollection 2022.
Epithelial mesenchymal transition (EMT) is closely related to the occurrence, development, metastasis and antitumor immunity of tumors. However, comprehensive studies correlating EMT and prognosis, tumor microenvironment (TME) and molecular subtypes of bladder cancer (BLCA) are lacking.
TCGA-BLCA was chosen as our training cohort, while Xiangya cohort, GSE13507, GSE48075 were selected as our validation cohorts. Prognostic genes were screened out using univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. Then we developed an EMT risk score based on these prognostic genes and systematically correlated the risk score with prognosis, TME and molecular subtypes of BLCA.
Based on EMT related genes, we developed two different EMT patterns, named EMT cluster 1 and cluster 2, and found that cluster 2 showed a worse prognosis and an inflammatory TME phenotype. For personalized prognosis and TME phenotypes predicting, we developed and validated an EMT-based risk score by 7 candidate genes (ANXA10, CNTN1, FAM180A, FN1, IGFL2, KANK4 and TOX3). Patients with high EMT risk scores had lower overall survival (OS) with high predictive accuracy both in the training cohort and validation cohort. In addition, we comprehensively correlated the EMT risk score with TME and molecular subtype, and found that high EMT risk score suggested higher levels of immune cell infiltration and more inclined to present the basal molecular subtype. It was noteworthy that the same results also appeared in the validation of Xiangya cohort.
EMT related genes play an important role in tumor progression and immunity in BLCA. Our EMT risk score could accurately predict prognosis and immunophenotype of a single patient, which could guide more effective precision medical strategies.
上皮间质转化（EMT）与肿瘤的发生、发展、转移和抗肿瘤免疫密切相关。然而，综合研究 EMT 与预后、肿瘤微环境（TME）和膀胱癌（BLCA）分子亚型的相关性还很缺乏。
选择 TCGA-BLCA 作为我们的训练队列，同时选择 Xiangya 队列、GSE48075 和 GSE48075 作为我们的验证队列。使用单因素 Cox 分析和最小绝对值收缩和选择算子（LASSO）算法筛选预后基因。然后，我们基于这些预后基因开发了一个 EMT 风险评分，并系统地将风险评分与 BLCA 的预后、TME 和分子亚型相关联。
基于 EMT 相关基因，我们开发了两种不同的 EMT 模式，分别命名为 EMT 簇 1 和簇 2，并发现簇 2显示出更差的预后和炎症性 TME 表型。为了进行个性化的预后和 TME 表型预测，我们基于 7 个候选基因（ANXA10、CNTN1、FAM180A、FN1、IGFL2、KANK4 和 TOX3）开发和验证了一个 EMT 风险评分。在训练队列和验证队列中，高 EMT 风险评分的患者总生存（OS）较低，具有较高的预测准确性。此外，我们全面地将 EMT 风险评分与 TME 和分子亚型相关联，发现高 EMT 风险评分提示免疫细胞浸润水平较高，更倾向于呈现基底分子亚型。值得注意的是，在 Xiangya 队列的验证中也出现了相同的结果。
EMT 相关基因在 BLCA 的肿瘤进展和免疫中发挥着重要作用。我们的 EMT 风险评分可以准确预测单个患者的预后和免疫表型，这可以指导更有效的精准医疗策略。
