Single-cell landscape and spatial transcriptomic analysis reveals macrophage infiltration and glycolytic metabolism in kidney renal clear cell carcinoma

被引:0
|
作者
Wen, Chen-Yueh [1 ]
Hsiao, Jui-Hu [2 ]
Tzeng, Yen-Dun Tony [3 ,4 ]
Chang, Renin [5 ]
Tsang, Yi-Ling [6 ,7 ]
Kuo, Chen-Hsin [8 ]
Li, Chia-Jung [9 ,10 ]
机构
[1] Kaohsiung Vet Gen Hosp, Dept Surg, Div Urol, Kaohsiung 813, Taiwan
[2] Kaohsiung Municipal Minsheng Hosp, Dept Surg, Kaohsiung 802, Taiwan
[3] Kaohsiung Vet Gen Hosp, Dept Surg, Kaohsiung 813, Taiwan
[4] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 804, Taiwan
[5] Kaohsiung Vet Gen Hosp, Dept Emergency Med, Kaohsiung 802, Taiwan
[6] Univ Munster, Inst Physiol Chem & Pathobiochem, D-48149 Munster, Germany
[7] Univ Munster, Cells Mot Interfac Ctr CiMIC, D-48149 Munster, Germany
[8] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan
[9] Kaohsiung Vet Gen Hosp, Dept Obstet & Gynecol, Kaohsiung 813, Taiwan
[10] Natl Sun Yat Sen Univ, Inst BioPharmaceut Sci, Kaohsiung 804, Taiwan
来源
AGING-US | 2023年 / 15卷 / 20期
关键词
PGAM1; glycolytic metabolism; immune infiltration; single cell-RNA sequencing; kidney renal clear cell carcinoma; COLORECTAL-CANCER;
D O I
暂无
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The present study investigates the clinical relevance of glycolytic factors, specifically PGAM1, in the tumor microenvironment of kidney renal clear cell carcinoma (KIRC). Despite the established role of glycolytic metabolism in cancer pathophysiology, the prognostic implications and key targets in KIRC remain elusive. We analyzed GEO and TCGA datasets to identify DEGs in KIRC and studied their relationship with immune gene expression, survival, tumor stage, gene mutations, and infiltrating immune cells. We explored Pgam1 gene expression in different kidney regions using spatial transcriptomics after mouse kidney injury analysis. Single cell RNA-sequencing was used to assess the association of PGAM1 with immune cells. Findings were validated with tumor specimens from 60 KIRC patients, correlating PGAM1 expression with clinicopathological features and prognosis using bioinformatics and immunohistochemistry. We demonstrated the expression of central gene regulators in renal cancer in relation to genetic variants, deletions, and tumor microenvironment. Mutations in these hub genes were positively associated with distinct immune cells in six different immune datasets and played a crucial role in immune cell infiltration in KIRC. Single-cell RNA-sequencing revealed that elevated PGAM1 was associated with immune cell infiltration, specifically macrophages. Furthermore, pharmacogenomic analysis of renal cancer cell lines indicated that inactivation of PGAM1 was associated with increased sensitivity to specific small-molecule drugs. Altered PGAM1 in KIRC is associated with disease progression and immune microenvironment. It has diagnostic and prognostic implications, indicating its potential in precision medicine and drug screening.
引用
收藏
页码:11298 / 11312
页数:15
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