Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Engineering Research Center of Natural Polymer-based Medical Materials in Hubei Province, Wuhan, Hubei, 430071, China.
The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, China.
Mol Genet Genomics. 2024 Jul 17;299(1):70. doi: 10.1007/s00438-024-02156-z.
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs) are a special type of fibroblasts, which play an important role in the development and immune escape of tumors. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression module. In combination with univariate Cox regression and analysis of least absolute shrinkage operator (LASSO), characteristics associated with CAFs were developed for a prognostic model. The migration and proliferation of lung cancer cells were evaluated in vitro. Finally, the expression levels of proteins were analyzed by Western blot. LASSO Cox regression algorithm was then performed to select hub genes. Finally, a total of 2 Genes (COL5A2, COL6A2) were obtained. We then divided LUAD patients into high- and low-risk groups based on CAFs risk scores. Survival analysis, CAFs score correlation analysis and tumor mutation load analysis showed that COL5A2 and COL6A2 were high-risk genes for LUAD. Human Protein Atlas (HPA), western blot and PCR results showed that COL5A2 and COL6A2 were up-regulated in LUAD tissues. When COL5A2 and COL6A2 were knocked down, the proliferation, invasion and migration of lung cancer cells were significantly decreased. Finally, COL5A2 can affect LUAD progression through the Wnt/β-Catenin and TGF-β signaling pathways. Our CAFs risk score model offers a new approach for predicting the prognosis of LUAD patients. Furthermore, the identification of high-risk genes COL5A2 and COL6A2 and drug sensitivity analysis can provide valuable candidate clues for clinical treatment of LUAD.
肺腺癌（LUAD）是全球癌症相关死亡的主要原因。癌症相关成纤维细胞（CAFs）是一种特殊类型的成纤维细胞，在肿瘤的发生和免疫逃逸中发挥重要作用。采用加权基因共表达网络分析（WGCNA）构建共表达模块。结合单变量Cox 回归和最小绝对值收缩和选择算子（LASSO）分析，开发了与 CAFs 相关的特征，用于预后模型。体外评估肺癌细胞的迁移和增殖。最后，通过 Western blot 分析蛋白质的表达水平。然后，通过 LASSO Cox 回归算法选择枢纽基因。最后，得到了 2 个基因（COL5A2、COL6A2）。然后，我们根据 CAFs 风险评分将 LUAD 患者分为高风险和低风险组。生存分析、CAFs 评分相关性分析和肿瘤突变负荷分析表明，COL5A2 和 COL6A2 是 LUAD 的高危基因。人类蛋白质图谱（HPA）、Western blot 和 PCR 结果表明，COL5A2 和 COL6A2 在 LUAD 组织中上调。当敲低 COL5A2 和 COL6A2 时，肺癌细胞的增殖、侵袭和迁移明显减少。最后，COL5A2 通过 Wnt/β-Catenin 和 TGF-β 信号通路影响 LUAD 的进展。我们的 CAFs 风险评分模型为预测 LUAD 患者的预后提供了一种新方法。此外，高风险基因 COL5A2 和 COL6A2 的鉴定和药物敏感性分析可以为 LUAD 的临床治疗提供有价值的候选线索。
