Xu Hengyi, Leng Jingze, Liu Fengshuo, Chen Tianxiang, Qu Jiangming, Yang Yufan, Ning Chun, Ke Xindi, Xiao Bin, Zhang Yanbin, Sun Lejia
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China.
Heliyon. 2024 Sep 23;10(19):e38310. doi: 10.1016/j.heliyon.2024.e38310. eCollection 2024 Oct 15.
Despite reported influences of the intratumoral microbiome on cancer progression, its role in this subtype remains unclear. This study aimed to characterize the microbial landscape and signatures of kidney renal clear cell carcinoma using RNA-Seq data from The Cancer Genome Atlas. Following microbial decontamination, differential microbial analysis was conducted between tumorous and adjacent non-tumorous samples. Compared to non-tumorous samples, tumorous microbiota exhibited reduced α and β diversity and distinct phylum-level communities. Differential microbial analysis between patients exhibiting long and short overall survival revealed ten significant differential microbial genera, with six genera correlating with a positive prognosis () and four with a negative prognosis (). Employing Cox regression analysis and support vector machines, a prognosis-related microbiome risk signature was developed, achieving an AUC of 0.809. Based on this risk signature, two microbiome-based subtypes were found to be significantly associated with distinct clinical prognoses and immune microenvironments. These findings were corroborated by significant correlations between prognostic-relevant microorganisms and 30 immune-related differentially expressed genes. Specifically, microbial genera associated with a negative prognosis were linked to a pro-tumor acute inflammatory immune response, whereas genera related to a positive prognosis were associated with an anti-tumor adaptive immune response. In conclusion, microbiome-based subtyping revealed correlations between tumor microbiome, clinical prognosis, and tumor microenvironment, indicating intratumoral microbiota as a promising prognostic biomarker for kidney renal clear cell carcinoma.
尽管有报道称肿瘤内微生物群对癌症进展有影响，但其在这种亚型中的作用仍不清楚。本研究旨在利用来自癌症基因组图谱的RNA测序数据，描绘肾透明细胞癌的微生物格局和特征。在进行微生物净化后，对肿瘤样本和相邻的非肿瘤样本进行了差异微生物分析。与非肿瘤样本相比，肿瘤微生物群的α和β多样性降低，且门水平的群落不同。对总生存期长和短的患者进行差异微生物分析，发现了10个显著差异的微生物属，其中6个属与预后良好相关，4个属与预后不良相关。采用Cox回归分析和支持向量机，建立了一个与预后相关的微生物组风险特征，曲线下面积为0.809。基于这一风险特征，发现两种基于微生物组的亚型与不同的临床预后和免疫微环境显著相关。预后相关微生物与30个免疫相关差异表达基因之间的显著相关性证实了这些发现。具体而言，与预后不良相关的微生物属与促肿瘤急性炎症免疫反应有关，而与预后良好相关的属与抗肿瘤适应性免疫反应有关。总之，基于微生物组的亚型分类揭示了肿瘤微生物组、临床预后和肿瘤微环境之间的相关性，表明肿瘤内微生物群是肾透明细胞癌一种有前景的预后生物标志物。
