Single-cell RNA-seq identification of the cellular molecular characteristics of sporadic bilateral clear cell renal cell carcinoma

Bilateral renal cell carcinoma (RCC) is a rare type of this disease and includes familial bilateral and sporadic bilateral RCCs. Studying the cellular molecular characteristics of sporadic bilateral is important to provide a direct guide for clinical treatment. These cellular molecular characteristics can be expressed at the RNA level, especially at the single-cell RNA level. Single-cell RNA sequencing (scRNA-seq) was performed on bilateral clear cell RCC (ccRCC). A total of 3,575 and 3,568 high-quality single-cell transcriptome data were captured from the left and right tumour tissues, respectively. Gene characteristics were identified by comparing left and right tumours at the scRNA level. This work presented the complex cellular environment of bilateral ccRCC by scRNA-seq. Single-cell transcriptome analysis revealed high similarity in gene expression among most cell types of bilateral RCCs but significant differences in gene expression among different site tumour cells. Additionally, the potential biological function of different tumour cell types was determined by gene ontology (GO) analysis. The transcriptome characteristics of tumour tissues in different locations at the single-cell transcriptome level were revealed through the scRNA-seq of bilateral sporadic ccRCC. This work provides new insights into the diagnosis and treatment of bilateral RCC.

双侧肾细胞癌（renal cell carcinoma, RCC）是该疾病的罕见亚型，涵盖家族性双侧肾细胞癌与散发性双侧肾细胞癌两类。针对散发性双侧肾细胞癌的细胞分子特征展开研究，可为临床治疗提供直接指导，具有重要意义。此类细胞分子特征可在RNA层面得以体现，尤以单细胞RNA层面最为显著。本研究针对双侧透明细胞肾细胞癌（clear cell RCC, ccRCC）开展了单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），分别从双侧肿瘤组织中获取了3575条与3568条高质量单细胞转录组数据。通过在单细胞RNA测序层面比对双侧肿瘤，研究者鉴定出了相关基因特征。本研究通过单细胞RNA测序技术，揭示了双侧透明细胞肾细胞癌复杂的细胞微环境。单细胞转录组分析结果显示，双侧肾细胞癌多数细胞类型的基因表达水平高度相似，但不同部位的肿瘤细胞基因表达存在显著差异。此外，本研究通过基因本体论（gene ontology, GO）分析，明确了不同肿瘤细胞类型的潜在生物学功能。通过对双侧散发性透明细胞肾细胞癌开展单细胞RNA测序，本研究揭示了不同部位肿瘤组织在单细胞转录组层面的转录组特征。本研究为双侧肾细胞癌的诊疗提供了全新的视角。