Xu Hongqiu, Du Wenqiang, Jing Xuelong, Xie Jingen, Li Pengfei
Department of General Medicine, Huai'an Hospital of Huai'an City, Huai'an City, Jiangsu Province, China.
Biotechnol Appl Biochem. 2024 Aug;71(4):817-834. doi: 10.1002/bab.2579. Epub 2024 Mar 12.
Despite the progress made in the management of lung adenocarcinoma (LUAD), the overall prognosis for LUAD individuals remains suboptimal. While the role of cell polarity in tumor invasion and metastasis is well established, its prognostic significance in LUAD is still unknown. Differential analysis was performed on the Cancer Genome Atlas (TCGA)-LUAD and normal lung tissue, and candidate genes were identified by intersecting differentially expressed genes with polarity-related genes (PRGs). A prognostic model was constructed using univariate and multivariate Cox regression and LASSO regression. To enhance the robustness of the analysis, an independent prognostic analysis was conducted by incorporating relevant clinical information. The accuracy and sensitivity of the model were validated using survival analysis and ROC curves. Finally, immune landscape, immune therapy, tumor mutation burden, and drug sensitivity analysis were carried out on high- and low-risk patients. Ten prognostic genes were screened to divide LUAD patients into different risk groups. Survival analysis, ROC curves, and univariate/multivariate Cox regression analyses collectively demonstrated the favorable predictive performance of the model, which could be an independent prognostic factor. The nomogram, in conjunction with the calibration curve, demonstrated the model's compelling predictive capacity in prognosticating the overall survival of LUAD individuals. Low-risk LUAD patients exhibited heightened levels of immune cell infiltration, immune scores, and immune checkpoint expression compared to high-risk individuals. So, they may have a greater likelihood of benefiting from immune therapy. The high-risk group demonstrated a remarkably higher tumor mutation burden (TMB) in contrast with the low-risk group. XAV-939, Fulvestrant, and SR16157 may have potential value in the clinical use of LUAD. We revealed the potential linkage between PRGs and LUAD prognosis, and the application of these prognostic factors in risk stratification and prognosis prediction of LUAD patients may be of great significance.
尽管在肺腺癌（LUAD）的治疗方面取得了进展，但LUAD患者的总体预后仍然不尽人意。虽然细胞极性在肿瘤侵袭和转移中的作用已得到充分证实，但其在LUAD中的预后意义仍不明确。对癌症基因组图谱（TCGA）-LUAD和正常肺组织进行差异分析，并通过将差异表达基因与极性相关基因（PRGs）相交来鉴定候选基因。使用单变量和多变量Cox回归以及LASSO回归构建预后模型。为了提高分析的稳健性，通过纳入相关临床信息进行独立预后分析。使用生存分析和ROC曲线验证模型的准确性和敏感性。最后，对高风险和低风险患者进行免疫景观、免疫治疗、肿瘤突变负担和药物敏感性分析。筛选出10个预后基因，将LUAD患者分为不同风险组。生存分析、ROC曲线以及单变量/多变量Cox回归分析共同证明了该模型具有良好的预测性能，可作为独立的预后因素。列线图结合校准曲线，证明了该模型在预测LUAD患者总生存方面具有强大的预测能力。与高风险个体相比，低风险LUAD患者表现出更高水平的免疫细胞浸润、免疫评分和免疫检查点表达。因此，他们可能更有可能从免疫治疗中获益。与低风险组相比，高风险组的肿瘤突变负担（TMB）明显更高。XAV-939、氟维司群和SR16157在LUAD的临床应用中可能具有潜在价值。我们揭示了PRGs与LUAD预后之间的潜在联系，这些预后因素在LUAD患者的风险分层和预后预测中的应用可能具有重要意义。
