Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of Thyroid and Breast Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Human Normal University, Changsha, 410008, China.
Sci Rep. 2024 Sep 27;14(1):22263. doi: 10.1038/s41598-024-73274-2.
ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies.
ATAD2（ATPase Family AAA Domain-Containing 2）在各种肿瘤类型中均高度表达，但它在肿瘤进展和免疫相互作用中的常见作用仍不清楚。我们利用 TCGA、GTEx、CPTAC、HPA 和 cBioPortal 数据库，分析了 ATAD2 的表达和改变谱及其在泛癌中的诊断和预后作用。此外，我们利用单细胞测序数据和 TCGA 数据库研究了 ATAD2 与免疫浸润之间的关系。此外，通过 MTT、划痕愈合、transwell 和流式细胞术检测，在甲状腺乳头状癌（PTC）中验证了 ATAD2 的表达和致癌功能。我们的结果表明，ATAD2 在大多数癌症中存在明显过表达，与预后不良密切相关。扩增是 ATAD2 最常见的改变类型，其突变与总生存期的改善相关。ATAD2 与多种抑制性免疫检查点呈正相关，并与免疫抑制微环境密切相关，尤其是在 PTC 中。体外实验表明，ATAD2 通过激活 PI3K-AKT 通路和调节 G1/S 细胞周期检查点，促进 PTC 细胞的增殖、迁移和侵袭。总之，ATAD2 有望成为泛癌诊断和预后的生物标志物，预测免疫治疗反应的生物标志物，以及增强现有抗肿瘤免疫治疗效果的治疗靶点。
