Zeng Zhen, Zuo Yuanli, Jin Yang, Peng Yong, Zhu Xiaofeng
Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Front Genet. 2022 May 30;13:872380. doi: 10.3389/fgene.2022.872380. eCollection 2022.
The extracellular matrix (ECM) is vital to normal cellular function and has emerged as a key factor in cancer initiation and metastasis. However, the prognostic and oncological values of ECM organization-related genes have not been comprehensively explored in lung adenocarcinoma (LUAD) patients. In this study, we included LUAD samples from The Cancer Genome Atlas (TCGA, training set) and other three validation sets (GSE87340, GSE140343 and GSE115002), then we constructed a three-gene prognostic signature based on ECM organization-related genes. The prognostic signature involving , and was powerful and robust in both the training and validation datasets. We further constructed a composite prognostic nomogram to facilitate clinical practice by integrating an ECM organization-related signature with clinical characteristics, including age and TNM stage. Patients with higher risk scores were characterized by proliferation, metastasis and immune hallmarks. It is worth noting that high-risk group showed higher fibroblast infiltration in tumor tissue. Accordingly, factors (, and ) reported to be secreted by cancer-associated fibroblasts (CAFs) showed higher expression level in the high-risk group. Our findings highlight the prognostic value of the ECM organization signature in LUAD and provide insights into the specific clinical and molecular features underlying the ECM organization-related signature, which may be important for patient treatment.
细胞外基质（ECM）对正常细胞功能至关重要，并且已成为癌症发生和转移的关键因素。然而，ECM组织相关基因的预后和肿瘤学价值在肺腺癌（LUAD）患者中尚未得到全面探索。在本研究中，我们纳入了来自癌症基因组图谱（TCGA，训练集）和其他三个验证集（GSE87340、GSE140343和GSE115002）的LUAD样本，然后基于ECM组织相关基因构建了一个三基因预后特征。涉及 、 和 的预后特征在训练和验证数据集中均强大且稳健。我们进一步构建了一个综合预后列线图，通过将ECM组织相关特征与临床特征（包括年龄和TNM分期）相结合来促进临床实践。风险评分较高的患者具有增殖、转移和免疫特征。值得注意的是，高风险组在肿瘤组织中显示出更高的成纤维细胞浸润。因此，据报道由癌症相关成纤维细胞（CAFs）分泌的因子（ 、 和 ）在高风险组中显示出更高的表达水平。我们的研究结果突出了ECM组织特征在LUAD中的预后价值，并为ECM组织相关特征背后的特定临床和分子特征提供了见解，这可能对患者治疗很重要。
