Department of Targeting Therapy & Immunology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Oncol Res. 2023 Sep 15;31(6):967-988. doi: 10.32604/or.2023.042309. eCollection 2023.
Lung adenocarcinoma (LUAD) is the most common and deadliest subtype of lung cancer. To select more targeted and effective treatments for individuals, further advances in classifying LUAD are urgently needed. The number, type, and function of T cells in the tumor microenvironment (TME) determine the progression and treatment response of LUAD. Long noncoding RNAs (lncRNAs), may regulate T cell differentiation, development, and activation. Thus, our aim was to identify T cell-related lncRNAs (T cell-Lncs) in LUAD and to investigate whether T cell-Lncs could serve as potential stratifiers and therapeutic targets. Seven T cell-Lncs were identified to further establish the T cell-related lncRNA risk score (TRS) in LUAD. Low TRS individuals were characterized by robust immune status, fewer genomic alterations, and remarkably longer survival than high TRS individuals. The excellent accuracy of TRS in predicting overall survival (OS) was validated in the TCGA-LUAD training cohort and the GEO-LUAD validation cohort. Our data demonstrated the favorable predictive power of the TRS-based nomogram, which had important clinical significance in estimating the survival probability for individuals. In addition, individuals with low TRS could respond better to chemotherapy and immunotherapy than those with high TRS. LINC00525 was identified as a valuable study target, and the ability of LUAD to proliferate or invade was significantly attenuated by downregulation of LINC00525. In conclusion, the TRS established by T cell-Lncs could unambiguously classify LUAD patients, predict their prognosis and guide their management. Moreover, our identified T cell-Lncs could provide potential therapeutic targets for LUAD.
肺腺癌 (LUAD) 是最常见和最致命的肺癌亚型。为了为个体选择更有针对性和更有效的治疗方法，迫切需要在 LUAD 分类方面取得进一步进展。肿瘤微环境 (TME) 中 T 细胞的数量、类型和功能决定了 LUAD 的进展和治疗反应。长链非编码 RNA (lncRNA) 可能调节 T 细胞分化、发育和激活。因此，我们的目的是鉴定 LUAD 中的 T 细胞相关 lncRNA (T 细胞-Lnc)，并研究 T 细胞-Lnc 是否可以作为潜在的分层和治疗靶点。鉴定了 7 个 T 细胞-Lnc 来进一步建立 LUAD 中的 T 细胞相关 lncRNA 风险评分 (TRS)。低 TRS 个体的免疫状态较强，基因组改变较少，生存时间明显长于高 TRS 个体。TRS 在 TCGA-LUAD 训练队列和 GEO-LUAD 验证队列中预测总生存期 (OS) 的准确性得到了验证。我们的数据表明，基于 TRS 的列线图具有良好的预测能力，对个体生存概率的估计具有重要的临床意义。此外，与高 TRS 个体相比，低 TRS 个体对化疗和免疫治疗的反应更好。LINC00525 被确定为有价值的研究靶点，下调 LINC00525 可显著减弱 LUAD 的增殖或侵袭能力。总之，由 T 细胞-Lnc 建立的 TRS 可以明确地对 LUAD 患者进行分类，预测他们的预后，并指导他们的管理。此外，我们鉴定的 T 细胞-Lnc 可以为 LUAD 提供潜在的治疗靶点。
