Lung cancer center, West China hospital, Sichuan university, Chengdu, China.
Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
J Cell Mol Med. 2024 Apr;28(8):e18262. doi: 10.1111/jcmm.18262.
Lung squamous cell carcinoma (LUSC) is one of the subtypes of lung cancer (LC) that contributes to approximately 25%-30% of its prevalence. Cancer-associated fibroblasts (CAFs) are key cellular components of the TME, and the large number of CAFs in tumour tissues creates a favourable environment for tumour development. However, the function of CAFs in the LUSC is complex and uncertain. First, we processed the scRNA-seq data and classified distinct types of CAFs. We also identified prognostic CAFRGs using univariate Cox analysis and conducted survival analysis. Additionally, we assessed immune cell infiltration in CAF clusters using ssGSEA. We developed a model with a significant prognostic correlation and verified the prognostic model. Furthermore, we explored the immune landscape of LUSC and further investigated the correlation between malignant features and LUSC. We identified CAFs and classified them into three categories: iCAFs, mCAFs and apCAFs. The survival analysis showed a significant correlation between apCAFs and iCAFs and LUSC patient prognosis. Kaplan-Meier analysis showed that patients in CAF cluster C showed a better survival probability compared to clusters A and B. In addition, we identified nine significant prognostic CAFRGs (CLDN1, TMX4, ALPL, PTX3, BHLHE40, TNFRSF12A, VKORC1, CST3 and ADD3) and subsequently employed multivariate Cox analysis to develop a signature and validate the model. Lastly, the correlation between CAFRG and malignant features indicates the potential role of CAFRG in promoting tumour angiogenesis, EMT and cell cycle alterations. We constructed a CAF prognostic signature for identifying potential prognostic CAFRGs and predicting the prognosis and immunotherapeutic response for LUSC. Our study may provide a more accurate prognostic assessment and immunotherapy targeting strategies for LUSC.
肺鳞状细胞癌（LUSC）是肺癌（LC）的一种亚型，约占其发病率的 25%-30%。癌症相关成纤维细胞（CAFs）是 TME 的关键细胞成分，肿瘤组织中大量的 CAFs 为肿瘤的发展创造了有利的环境。然而，CAFs 在 LUSC 中的功能是复杂和不确定的。首先，我们处理了 scRNA-seq 数据，并对不同类型的 CAFs 进行了分类。我们还使用单变量 Cox 分析确定了预后 CAFRGs，并进行了生存分析。此外，我们使用 ssGSEA 评估了 CAF 簇中的免疫细胞浸润。我们建立了一个具有显著预后相关性的模型，并验证了该预后模型。此外，我们还研究了 LUSC 的免疫图谱，并进一步探讨了恶性特征与 LUSC 的相关性。我们鉴定了 CAFs 并将其分为三类：iCAFs、mCAFs 和 apCAFs。生存分析显示 apCAFs 与 iCAFs 与 LUSC 患者预后有显著相关性。Kaplan-Meier 分析显示，CAF 簇 C 中的患者比簇 A 和簇 B 的生存概率更高。此外，我们鉴定了 9 个有显著预后意义的 CAFRGs（CLDN1、TMX4、ALPL、PTX3、BHLHE40、TNFRSF12A、VKORC1、CST3 和 ADD3），并随后采用多变量 Cox 分析构建了一个 signature 并验证了该模型。最后，CAFRG 与恶性特征的相关性表明 CAFRG 在促进肿瘤血管生成、EMT 和细胞周期改变方面的潜在作用。我们构建了一个 CAF 预后signature，用于识别潜在的预后 CAFRGs，并预测 LUSC 的预后和免疫治疗反应。我们的研究可能为 LUSC 提供更准确的预后评估和免疫治疗靶向策略。
