PO.TB10.07 · 肿瘤生物学
TSC相关血管平滑肌脂肪瘤的空间转录组解析揭示由mTORC1失调驱动的微环境程序
Spatial transcriptomic dissection of TSC-associated angiomyolipoma reveals microenvironmental programs driven by mTORC1 dysregulation
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作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景
结节性硬化症相关血管平滑肌脂肪瘤(TSC-AML)常见于年轻患者,呈多灶性和大肿瘤,导致出血和肾功能障碍等临床并发症。尽管TSC1/TSC2缺失所致的mTORC1激活已被认识,但其空间组织化的转录结构以及与散发性AML的差异仍不明确。本研究应用空间转录组学来表征TSC-AML结构背后的分子特征。
方法
使用10x Genomics CytAssist Visium平台,对TSC-AML、散发性AML和肾细胞癌(RCC)各1例的福尔马林固定石蜡包埋切片进行分析。进行聚类、差异表达和通路分析,以识别空间转录模式和TSC-AML特异性特征。
结果
空间基因表达图谱显示,TSC-AML和散发性AML共有由血管、平滑肌和脂肪成分构成的经典三相结构,与PEC谱系起源一致,而RCC则呈现不同的上皮谱。TSC-AML表现出TSC1/TSC2表达降低,伴MTOR、MLST8和RPTOR轻度上调,提示mTORC1通路失调。比较分析识别出42个在TSC-AML中特异性上调的基因,包括神经发育相关(GRIA2、ASTN1)、脂质代谢相关(FABP4、APOC1)、结构相关(LDB3、SYNM)和免疫调节相关(IL33、ABCC8)基因。这些转录差异代表了区分TSC-AML与散发性AML的潜在分子特征。空间图谱进一步凸显了肿瘤内异质性以及基因表达随结构成分而变化的特点。
结论
尽管存在单一病例的局限,本研究提供了TSC-AML的详细空间转录组图谱,揭示了与TSC1/TSC2功能障碍相关的转录程序并识别出TSC-AML特异性基因特征。这些发现提供了候选生物标志物和治疗靶点,并为未来旨在完善分子表征、改善TSC相关肾肿瘤临床管理的多病例研究奠定了基础。
查看英文原文 English abstract
Background
Tuberous sclerosis complex-associated angiomyolipoma (TSC-AML) frequently presents in young patients with multifocal and large tumors, leading to clinical complications such as hemorrhage and renal dysfunction. Although mTORC1 activation due to TSC1/TSC2 loss is recognized, the spatially organized transcriptional architecture and differences from sporadic AML remain unclear. This study applied spatial transcriptomics to characterize molecular features underlying TSC-AML structure.
Methods
Formalin-fixed, paraffin-embedded sections from one case each of TSC-AML, sporadic AML, and renal cell carcinoma (RCC) were analyzed using the 10x Genomics CytAssist Visium platform. Clustering, differential expression, and pathway analyses were performed to identify spatial transcriptional patterns and TSC-AML-specific signatures.
Results
Spatial gene expression maps showed that TSC-AML and sporadic AML shared the classic triphasic architecture of vascular, smooth muscle, and adipose components, consistent with a PEC lineage origin, whereas RCC displayed a distinct epithelial profile.TSC-AML demonstrated reduced TSC1/TSC2 expression with mild upregulation of MTOR, MLST8, and RPTOR, indicating mTORC1 pathway dysregulation.Comparative analysis identified 42 genes specifically upregulated in TSC-AML, including neurodevelopment-related (GRIA2, ASTN1), lipid metabolism-associated (FABP4, APOC1), structural (LDB3, SYNM), and immune-regulatory (IL33, ABCC8) genes. These transcriptional differences represent potential molecular features distinguishing TSC-AML from sporadic AML.Spatial mapping further highlighted intratumoral heterogeneity and structural component-dependent variation in gene expression.
Conclusions
Despite the single-case limitation, this study provides a detailed spatial transcriptomic profile of TSC-AML, revealing transcriptional programs linked to TSC1/TSC2 dysfunction and identifying TSC-AML-specific gene signatures. These findings offer candidate biomarkers and therapeutic targets and establish a foundation for future multi-case studies aimed at refining molecular characterization and improving clinical management of TSC-associated renal tumors.
利益披露 Disclosure
R. Watanabe, None..
K. Shishido, None..
S. Nobumori, None..
N. Sugihara, None..
K. Nishida, None..
H. Arai, None..
T. Sawada, None..
S. Haga, None..
O. Arai, None..
T. Onishi, None..
K. Nishimura, None..
T. Fukumoto, None..
N. Miura, None..
M. Kurara, None..
R. Kitazawa, None..
Y. Miyauchi, None..
T. Kikugawa, None..
T. Saika, None.