Wang Jinjie, Zhu Jiaqi, Tang Yijie, Zhang Anping, Zhou Tingting, Zhou Youlang, Shi Jiahai
Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu, China.
J Oncol. 2022 Sep 13;2022:3528142. doi: 10.1155/2022/3528142. eCollection 2022.
Recently, a large number of studies have sought personalized treatment for lung squamous cell carcinoma (LUSC) by dividing patients into different molecular subtypes. Autophagy plays an important role in maintaining the tumor microenvironment and immune-related biological processes. However, the molecular subtypes mediated by autophagy in LUSC are not clear.
Based on 490 LUSC samples, we systematically analyzed the molecular subtype modification patterns mediated by autophagy-related genes. The ssGSEA and CIBERSORT algorithm were utilized to quantify the relative abundance of TME cell infiltration. Principal component analysis was used to construct autophagy prognostic score (APS) model.
We identified three autophagy subtypes in LUSC, and their clinical outcomes and TME cell infiltration had significant heterogeneity. Cluster A was rich in immune cell infiltration. The enrichment of EMT stromal pathways and immune checkpoint molecules were significantly enhanced, which may lead to its immunosuppression. Cluster B was characterized by relative immunosuppression and relative stromal activation. Cluster C was activated in biological processes related to repair. Patients with high APS were significantly positively correlated with TME stromal activity and poor survival. Meanwhile, high APS showed an advantage in response to anti-PD1 and anti-CTLA4 immunotherapy.
This study explored the autophagy molecular subtypes in LUSC. We also discovered the heterogeneity of TME cell infiltration driven by autophagy-related genes. The established APS model is of great significance for evaluating the prognosis of LUSC patients, the infiltration of TME cells, and the effect of immunotherapy.
近年来，大量研究试图通过将患者分为不同分子亚型来寻求肺鳞状细胞癌（LUSC）的个性化治疗。自噬在维持肿瘤微环境和免疫相关生物学过程中发挥着重要作用。然而，LUSC中由自噬介导的分子亚型尚不清楚。
基于490例LUSC样本，我们系统分析了自噬相关基因介导的分子亚型改变模式。利用单样本基因集富集分析（ssGSEA）和CIBERSORT算法量化肿瘤微环境（TME）细胞浸润的相对丰度。采用主成分分析构建自噬预后评分（APS）模型。
我们在LUSC中鉴定出三种自噬亚型，它们的临床结局和TME细胞浸润具有显著异质性。A簇富含免疫细胞浸润。上皮-间质转化（EMT）基质途径和免疫检查点分子的富集显著增强，这可能导致其免疫抑制。B簇的特征是相对免疫抑制和相对基质激活。C簇在与修复相关的生物学过程中被激活。高APS患者与TME基质活性和较差的生存率显著正相关。同时，高APS在抗程序性死亡蛋白1（PD1）和抗细胞毒性T淋巴细胞相关蛋白4（CTLA4）免疫治疗反应中显示出优势。
本研究探索了LUSC中的自噬分子亚型。我们还发现了由自噬相关基因驱动的TME细胞浸润的异质性。所建立的APS模型对于评估LUSC患者的预后、TME细胞浸润以及免疫治疗效果具有重要意义。
