Chi Junpeng, Lou Keyuan, Zhang Jiankun, Wu Jitao, Cui Yuanshan
Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
School of Clinical Medicine, Shandong Second Medical University, Weifang, China.
Front Immunol. 2025 Apr 17;16:1542780. doi: 10.3389/fimmu.2025.1542780. eCollection 2025.
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis, and its clinical management remains a significant challenge due to the high recurrence rates and limited treatment options. Despite advances in understanding the molecular mechanisms underlying ACC, no reliable biomarkers have been validated for routine clinical use. METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) to investigate the expression of VGF in ACC and normal adrenal tissues. Gene expression levels of VGF were quantified and correlated with clinicopathological features and survival outcomes. Statistical methods included Cox proportional hazards models and Kaplan-Meier analysis, while Gene Set Enrichment Analysis (GSEA) was utilized to identify relevant biological pathways associated with VGF expression. Clinical data from 7 ACC patients from YANTAI YUHUANGDING Hospital were also analyzed. The expression of VGF in ACC and normal adrenal gland tissue was further validated through IHC experiments. RESULTS: Our results demonstrate that VGF expression is elevated in ACC tissues compared to normal adrenal tissues and is significantly associated with advanced disease stages, lymph node involvement, metastasis and poor overall survival. VGF levels also correlate with immune cell infiltration, including Th2 cells, T helper cells, and Neutrophils. Importantly, our study establishes VGF as a potential prognostic biomarker for ACC and highlights its role in tumor progression and immune modulation. Additionally, GSEA analysis suggests that VGF is involved in cytokine receptor interaction and the P13K-Akt signaling pathway, possibly relating to tumor immunity. CONCLUSIONS: VGF could serve as a valuable marker for patient stratification, monitoring disease progression, and predicting responses to immunotherapies. Future studies should focus on investigating circulating VGF levels as a non-invasive biomarker for ACC to improve clinical management and treatment outcomes.
背景：肾上腺皮质癌（ACC）是一种罕见且侵袭性强的恶性肿瘤，预后较差，由于其高复发率和有限的治疗选择，其临床管理仍然是一项重大挑战。尽管在理解ACC潜在分子机制方面取得了进展，但尚未有可靠的生物标志物被验证可用于常规临床应用。 方法：我们分析了来自癌症基因组图谱（TCGA）数据库（n = 79）和基因型组织表达（GTEx）数据库（n = 128）的RNA测序数据，以研究VGF在ACC和正常肾上腺组织中的表达。对VGF的基因表达水平进行定量，并将其与临床病理特征和生存结果相关联。统计方法包括Cox比例风险模型和Kaplan-Meier分析，同时利用基因集富集分析（GSEA）来识别与VGF表达相关的相关生物学途径。还分析了来自烟台毓璜顶医院的7例ACC患者的临床数据。通过免疫组化实验进一步验证了VGF在ACC和正常肾上腺组织中的表达。 结果：我们的结果表明，与正常肾上腺组织相比，VGF在ACC组织中的表达升高，并且与晚期疾病阶段、淋巴结受累、转移和总体生存率差显著相关。VGF水平还与免疫细胞浸润相关，包括Th2细胞、辅助性T细胞和中性粒细胞。重要的是，我们的研究将VGF确立为ACC的潜在预后生物标志物，并突出了其在肿瘤进展和免疫调节中的作用。此外，GSEA分析表明VGF参与细胞因子受体相互作用和P13K-Akt信号通路，可能与肿瘤免疫有关。 结论：VGF可作为患者分层、监测疾病进展和预测免疫治疗反应的有价值标志物。未来的研究应集中于研究循环VGF水平作为ACC的非侵入性生物标志物，以改善临床管理和治疗结果。
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