Multi-omics profiling highlights karyopherin subunit alpha 2 as a promising biomarker for prognosis and immunotherapy respond in pediatric and adult adrenocortical carcinoma

作者：Yi‐Hao Chen, Shumin Fang, Chuanfan Zhong, Shanshan Mo, Yongcheng Shi, Xiaohui Ling, Fengping Liu, Weide Zhong, Junhong Deng, Zhong Dong, Jia-Hong Chen, Jianming Lü · 发表于：Annals of Medicine · 年份：2024 · DOI：10.1080/07853890.2024.2397092 · 被引用次数：3 · 研究领域：Adrenal and Paraganglionic Tumors、Nuclear Structure and Function、Cancer, Hypoxia, and Metabolism

PURPOSE: Adrenocortical carcinoma (ACC) afflicts both pediatric and adult populations and is characterized by dismal prognosis and elevated mortality. Given the inconsistent therapeutic benefits and significant side effects associated with the conventional chemotherapy agent, mitotane, and the nascent stage of immunotherapy and targeted treatments, there is an urgent need to identify novel prognostic biomarkers and therapeutic targets in ACC. METHODS: Utilizing multi-omic datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we employed Weighted Gene Co-expression Network Analysis (WGCNA), Cox regression, Receiver Operating Characteristic (ROC) curves, and survival analyses to sift for potential prognostic biomarkers. We subsequently validated these findings through immunohistochemistry and cell assays, and delved into the biological role of KPNA2 in ACC through functional enrichment analysis, mutational landscape, and immune cell infiltration. RESULTS: A total of 77 progression-associated genes with aberrant chromosomal accessibility were discerned within the TCGA-ACC dataset. By integrating ROC and Cox regression from GEO datasets, KPNA2 emerged as an independent risk factor portending poor outcomes in ACC. ATAC-seq analysis revealed attenuated chromatin accessibility of KPNA2 in cases with unfavorable prognosis. Immunohistochemistry corroborated elevated KPNA2 expression, which was linked to enhanced proliferation and invasion. Elevated KPNA2 ...