2. Academic Validation
  3. A novel cancer-associated fibroblast signature for kidney renal clear cell carcinoma via integrated analysis of single-cell and bulk RNA-sequencing

A novel cancer-associated fibroblast signature for kidney renal clear cell carcinoma via integrated analysis of single-cell and bulk RNA-sequencing

  • Discov Oncol. 2024 Jul 26;15(1):309. doi: 10.1007/s12672-024-01175-x.
Ling Lu 1,  Huaguo Feng 2,  Guohua Dai 2,  Shuangquan Liu 2,  Yi Feng 3,  Haoyang Tan 2,  Xian Zhang 4,  Guoqing Hong # 5,  Xing Lai # 6 7
Affiliations

Affiliations

  • 1 Department of Renal Rheumatology Immunology, School of Medicine, Chongqing University Jiangjin Hospital, Chongqing University, Chongqing, China.
  • 2 Department of Hepatobiliary Surgery, School of Medicine, Chongqing University Jiangjin Hospital, Chongqing University, Chongqing, China.
  • 3 Department of Hepatobiliary Surgery, Jiangjin District Maternal and Child Health Hospital, Chongqing, China.
  • 4 Department of Hepatobiliary Surgery, Tongnan District People's Hospital, No. 189, Jianshe Road, Dafo Street, Tongnan District, Chongqing, China.
  • 5 Department of Hepatobiliary Surgery, Tongnan District People's Hospital, No. 189, Jianshe Road, Dafo Street, Tongnan District, Chongqing, China. 359933123@qq.com.
  • 6 Department of Hepatobiliary Surgery, Tongnan District People's Hospital, No. 189, Jianshe Road, Dafo Street, Tongnan District, Chongqing, China. lx8243495@163.com.
  • 7 Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. lx8243495@163.com.
  • # Contributed equally.
PMID: 39060620 DOI: 10.1007/s12672-024-01175-x
Abstract

Cancer-associated fibroblasts (CAFs), integral components of the tumor microenvironment, play a pivotal role in tumor proliferation, metastasis, and clinical outcomes. However, its specific roles in Kidney Renal Clear Cell Carcinoma (KIRC) remain poorly understood. Employing the established Seurat single-cell analysis pipeline, we identified 21 CAFs marker genes. Subsequently, a prognostic signature consisting of 6 CAFs marker genes (RGS5, PGF, TPM2, GJA4, SEPT4, and PLXDC1) was developed in a cohort through univariate and LASSO COX regression analyses. The model's efficacy was then validated in an external cohort, with a remarkable predictive performance in 1-, 3-, and 5-year. Patients in the high-risk group exhibited significantly inferior survival outcomes (p < 0.001), and the risk score was an independent prognostic factor (p < 0.05). Distinct differences in immune cell profiles and drug susceptibility were observed between the two risk groups. In KIRC, the PGF-VEGFR1 signaling pathway displayed a notable increase. PGF expression was significantly elevated in tumor tissues, as demonstrated by quantitative real-time polymerase chain reaction. In vitro, transwell assays and CCK8 revealed that recombinant-PGF could enhance the capability of cell proliferation, migration, and invasion in 769P and 786-O cells. This study firstly developed a novel predictive model based on 6 CAFs genes for KIRC. Additionally, PGF may present a potential therapeutic target to enhance KIRC treatment.

Keywords

Cancer-associated fibroblast; Kidney renal clear cell carcinoma; Prognosis signature; Single-cell RNA-sequencing.

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