Heterogeneity of tumor microenvironment is associated with clinical prognosis of non-clear cell renal cell carcinoma: a single-cell genomics study

被引:12
作者
Chen, Wen-jin [1 ]
Cao, Hao [2 ,3 ]
Cao, Jian-wei [4 ]
Zuo, Li [5 ]
Qu, Fa-jun [4 ]
Xu, Da [1 ]
Zhang, Hao [6 ]
Gong, Hai-yi [6 ]
Chen, Jia-xin [1 ]
Ye, Jian-qing [1 ]
Gan, Si-shun [1 ]
Zhou, Wang [1 ,4 ]
Zhu, Da-wei [5 ]
Pan, Xiu-Wu [1 ,4 ]
Cui, Xin-gang [1 ,4 ]
机构
[1] Second Mil Med Univ, Affiliated Hosp 3, Dept Urol, 700 North Moyu Rd, Shanghai 201805, Peoples R China
[2] Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Peoples R China
[3] Tsinghua Univ, Peking Tsinghua Ctr Life Sci, Beijing 100084, Peoples R China
[4] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Urol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[5] Nanjing Med Univ, Dept Urol, Affiliated Changzhou 2 Peoples Hosp, 29 Xinglong Rd, Changzhou 213000, Jiangsu, Peoples R China
[6] Second Mil Med Univ, Dept Orthoped Oncol, Changzheng Hosp, 415 Fengyang Rd, Shanghai 200003, Peoples R China
基金
中国国家自然科学基金;
关键词
INTRATUMORAL HETEROGENEITY; EXPRESSION; MANAGEMENT; PROTEIN;
D O I
10.1038/s41419-022-04501-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Non-clear renal cell carcinomas (nccRCCs) are less frequent in kidney cancer with histopathological heterogeneity. A better understanding of the tumor biology of nccRCC can provide more effective treatment paradigms for different subtypes. To reveal the heterogeneity of tumor microenvironment (TME) in nccRCC, we performed 10x sing-cell genomics on tumor and normal tissues from patients with papillary renal cell carcinoma (pRCC), chromophobe RCC (chrRCC), collecting duct carcinoma (CDRCC) and sarcomatoid RCC (sarRCC). 15 tissue samples were finally included. 34561 cells were identified as 16 major cell clusters with 34 cell subtypes. Our study presented the sing-cell landscape for four types of nccRCC, and demonstrated that CD8+ T cells exhaustion, tumor-associated macrophages (TAMs) and sarcomatoid process were the pivotal factors in immunosuppression of nccRCC tissues and were closely correlated with poor prognosis. Abnormal metabolic patterns were present in both cancer cells and tumor-infiltrating stromal cells, such as fibroblasts and endothelial cells. Combined with CIBERSORTx tool, the expression data of bulk RNA-seq from TCGA were labeled with cell types of our sing-cell data. Calculation of the relative abundance of cell types revealed that greater proportion of exhausted CD8+ T cells, TAMs and sarRCC derived cells were correlated with poor prognosis in the cohort of 274 nccRCC patients. To the best of our knowledge, this is the first study that provides a more comprehensive sight about the heterogeneity and tumor biology of nccRCC, which may potentially facilitate the development of more effective therapies for nccRCC.
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页数:14
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