Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, State Key Laboratory of Transvascular Implantation Devices, Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, P.R. China.
Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China
Cancer Genomics Proteomics. 2023 Sep-Oct;20(5):433-447. doi: 10.21873/cgp.20395.
BACKGROUND/AIM: SRY-box containing gene 17 (SOX17) plays a pivotal role in cancer onset and progression and is considered a potential target for cancer diagnosis and treatment. However, the expression pattern of SOX17 in cancer and its clinical relevance remains unknown. Here, we explored the relationship between the expression of SOX17 and drug response by examining SOX17 expression patterns across multiple cancer types.
Single-cell and bulk RNA-seq analyses were used to explore the expression profile of SOX17. Analysis results were verified with qPCR and immunohistochemistry. Survival, drug response, and co-expression analyses were performed to illustrate its correlation with clinical outcomes.
The results revealed that abnormal expression of SOX17 is highly heterogenous across multiple cancer types, indicating that SOX17 manifests as a cancer type-dependent feature. Furthermore, the expression pattern of SOX17 is also associated with cancer prognosis in certain cancer types. Strong SOX17 expression correlates with the potency of small molecule drugs that affect PI3K/mTOR signaling. FGF18, a gene highly relevant to SOX17, is involved in the PI3K-AKT signaling pathway. Single-cell RNA-seq analysis demonstrated that SOX17 is mainly expressed in endothelial cells and barely expressed in other cells but spreads to other cell types during the development of ovarian cancer.
Our study revealed the expression pattern of SOX17 in pan-cancer through bulk and single-cell RNA-seq analyses and determined that SOX17 is related to the diagnosis, staging, and prognosis of some tumors. These findings have clinical implications and may help identify mechanistic pathways amenable to pharmacological interventions.
背景/目的:性决定区 Y 框基因 17(SOX17)在癌症的发生和进展中起着关键作用,被认为是癌症诊断和治疗的潜在靶点。然而,SOX17 在癌症中的表达模式及其临床相关性尚不清楚。在这里,我们通过研究多种癌症类型中 SOX17 的表达模式,探讨了 SOX17 的表达与药物反应之间的关系。
使用单细胞和批量 RNA-seq 分析来探索 SOX17 的表达谱。使用 qPCR 和免疫组织化学验证分析结果。进行生存、药物反应和共表达分析,以说明其与临床结果的相关性。
结果表明,SOX17 在多种癌症类型中的异常表达高度异质,表明 SOX17 表现为癌症类型依赖性特征。此外,SOX17 的表达模式也与某些癌症类型的癌症预后相关。SOX17 表达强与影响 PI3K/mTOR 信号的小分子药物的效力相关。与 SOX17 高度相关的基因 FGF18 参与 PI3K-AKT 信号通路。单细胞 RNA-seq 分析表明,SOX17 主要在血管内皮细胞中表达,而在其他细胞中几乎不表达,但在卵巢癌的发展过程中扩散到其他细胞类型。
通过批量和单细胞 RNA-seq 分析,我们揭示了泛癌中 SOX17 的表达模式,并确定 SOX17 与一些肿瘤的诊断、分期和预后有关。这些发现具有临床意义,可能有助于确定可通过药物干预的机制途径。