文章：

透明细胞肾细胞癌中肿瘤细胞的空间分布与转移及基质组基因表达特征相关

Spatial Distribution of Tumor Cells in Clear Cell Renal Cell Carcinoma Is Associated with Metastasis and a Matrisome Gene Expression Signature

原文发布日期：14 January 2025

DOI: 10.3390/cancers17020249

类型: Article

开放获取: 是

英文摘要：

Background/Objectives:Predicting the behavior of clear cell renal cell carcinoma (ccRCC) is challenging using standard-of-care histopathologic examination. Indeed, pathologic RCC tumor grading, based on nuclear morphology, performs poorly in predicting outcomes of patients with International Society of Urological Pathology/World Health Organization grade 2 and 3 tumors, which account for most ccRCCs.Methods:We applied spatial point process modeling of H&E-stained images of patients with grade 2 and grade 3 ccRCCs (n= 72) to find optimum separation into two groups.Results:One group was associated with greater spatial randomness and clinical metastasis (p< 0.01). Notably, spatial analysis outperformed standard pathologic grading in predicting clinical metastasis. Moreover, cell-to-cell interaction distances in the metastasis-associated group were significantly greater than those in the other patient group and were also greater than expected by the random distribution of cells. Differential gene expression between the two spatially defined groups of patients revealed a matrisome signature, consistent with the extracellular matrix’s crucial role in tumor invasion. The top differentially expressed genes (with a fold change > 3) stratified a larger, multi-institutional cohort of 352 ccRCC patients from The Cancer Genome Atlas into groups with significant differences in survival and TNM disease stage.Conclusions:Our results suggest that the spatial distribution of ccRCC tumor cells can be extracted from H&E-stained images and that it is associated with metastasis and with extracellular matrix genes that are presumably driving these tumors’ aggressive behavior.

摘要翻译： 

背景/目的：利用标准组织病理学检查预测透明细胞肾细胞癌（ccRCC）的生物学行为具有挑战性。事实上，基于细胞核形态学的病理学肾细胞癌分级系统在预测国际泌尿病理学会/世界卫生组织2级和3级肿瘤（占ccRCC大多数）患者的临床结局方面表现欠佳。方法：我们对72例2级和3级ccRCC患者的H&E染色切片进行空间点过程建模，以寻找最佳的两组分类方案。结果：其中一组表现出更高的空间随机性且与临床转移显著相关（p<0.01）。值得注意的是，在预测临床转移方面，空间分析法的表现优于标准病理分级。此外，转移相关组的细胞间相互作用距离显著大于另一患者组，且超出细胞随机分布的预期范围。两组空间定义患者间的差异基因表达分析显示基质组特征，这与细胞外基质在肿瘤侵袭中的关键作用相符。差异最显著的基因（倍数变化>3）在癌症基因组图谱中352例多机构ccRCC患者队列中成功分层，各组间生存率和TNM分期存在显著差异。结论：我们的研究结果表明，ccRCC肿瘤细胞的空间分布特征可从H&E染色图像中提取，该特征与肿瘤转移及可能驱动侵袭行为的细胞外基质基因相关。

原文链接：

Spatial Distribution of Tumor Cells in Clear Cell Renal Cell Carcinoma Is Associated with Metastasis and a Matrisome Gene Expression Signature