Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
J Cancer Res Clin Oncol. 2023 Oct;149(13):11041-11055. doi: 10.1007/s00432-023-04980-z. Epub 2023 Jun 20.
According to previous reports, GTPase of immunity-associated protein 6 (GIMAP6) is essential for autophagy. However, it is unclear how GIMAP6 affects the development and tumor immunity of lung adenocarcinoma (LUAD).
In the present study, the role of GIMAP6 in vivo and in vitro was examined using reverse transcription-quantitative PCR, western blotting, and Cell Counting Kit-8, colony formation and Transwell assays. Datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases were thoroughly analyzed using R software. A nomogram was created using GIMAP6 and prognostic characteristics. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were applied to explore the potential mechanism of GIMAP6 in lung cancer. The link between GIMAP6 and the immunological landscape was studied using single-cell RNA sequencing datasets from Tumor Immune Estimation Resource (TIMER) 2.0 and Tumor Immune Single-cell Hub.
Patients with high GIMAP6 expression had improved overall and disease-specific survival compared with those patients with low GIMAP6 expression. According to the receiver operating characteristic and calibration curve, the nomogram based on T stage, N stage and GIMAP6 had predictive value for prognosis. According to functional enrichment analysis, GIMAP6 was primarily involved in T-cell receptor signaling pathway, chemokine signaling pathway, cytokine and cytokine receptor interaction. GIMAP6 was shown to be favorably linked with the infiltration of immune cells and immune-related molecules, including cytotoxic T-lymphocyte associated protein 4, programmed death-ligand 1, and T cell immunoreceptor with Ig and ITIM domains, by single-cell sequencing and TIMER2.0 analysis. The role of GIMAP6 in lung cancer cell proliferation, invasion, migration and immunity was experimentally verified.
These findings confirmed that GIMAP6 was an effective prognostic molecule that was involved in the regulation of the immune microenvironment of LUAD, and may become a predictor for the efficacy of immunotherapy.
根据之前的报道，免疫相关蛋白 6（GIMAP6）的 GTPase 对于自噬至关重要。然而，GIMAP6 如何影响肺腺癌（LUAD）的发展和肿瘤免疫仍不清楚。
在本研究中，通过逆转录定量 PCR、western blot 和细胞计数试剂盒-8、集落形成和 Transwell 测定，在体内和体外检测 GIMAP6 的作用。使用 R 软件对来自癌症基因组图谱和基因型组织表达数据库的数据集进行了深入分析。使用 GIMAP6 和预后特征创建了一个列线图。应用基因本体论、京都基因与基因组百科全书和基因集富集分析来探索 GIMAP6 在肺癌中的潜在机制。使用来自肿瘤免疫估计资源（TIMER）2.0 和肿瘤免疫单细胞中心的单细胞 RNA 测序数据集研究了 GIMAP6 与免疫景观之间的联系。
与 GIMAP6 低表达的患者相比，GIMAP6 高表达的患者总生存期和疾病特异性生存期均得到改善。根据接收者操作特征和校准曲线，基于 T 分期、N 分期和 GIMAP6 的列线图具有预后预测价值。根据功能富集分析，GIMAP6 主要参与 T 细胞受体信号通路、趋化因子信号通路、细胞因子和细胞因子受体相互作用。通过单细胞测序和 TIMER2.0 分析，GIMAP6 与免疫细胞和免疫相关分子（包括细胞毒性 T 淋巴细胞相关蛋白 4、程序性死亡配体 1 和 T 细胞免疫受体与 Ig 和 ITIM 结构域）的浸润呈正相关。实验验证了 GIMAP6 在肺癌细胞增殖、侵袭、迁移和免疫中的作用。
这些发现证实 GIMAP6 是一种有效的预后分子，参与 LUAD 免疫微环境的调节，可能成为免疫治疗疗效的预测因子。
