A multi-omics study of diagnostic markers and the unique inflammatory tumor micro-environment involved in tuberous sclerosis complex-related renal angiomyolipoma

Wang, Zhan and Xiaoyan, L. and Wenda, W. and Jing, W. and Seery, S. and Jiyu, X. and Haidan, S. and Yuncui, Y. and Yang, Z. and Xu, W. and Zhangcheng, L. and Yanan, L. and Wei, S. and Lulu, J. and Yushi, Z. (2022) A multi-omics study of diagnostic markers and the unique inflammatory tumor micro-environment involved in tuberous sclerosis complex-related renal angiomyolipoma. International Journal of Oncology, 61 (5).

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Abstract

Tuberous sclerosis complex (TSC) is a rare disease that threatens multiple organs in the human body. TSC-associated renal angiomyolipoma (TSC-RAML) has potentially life-threatening complications and a generally poor prognosis. The present study aimed to find plasma proteomic diagnostics and disease-associated markers, and explore the tumor microenvironment using multi-omics. To achieve this goal, the plasma proteomics as well as tissue proteomics, bulk and single-cell RNA transcriptome from patients with TSC-RAML were examined and analyzed. The results suggested that plasma proteins such as MMP9 and C-C motif chemokine ligand 5 were able to differentiate TSC-RAML from sporadic angiomyolipoma and renal cyst. A correlation analysis revealed that plasma proteomics were associated with lymphangioleiomyomatosis, TSC-RAML grading and whole-body disease burden. Tissue proteomics of participants with TSC-RAML revealed disturbed small molecule catabolic process, mitochondrial matrix component and actin binding function. Bulk and single-cell RNA sequencing suggested a greater number of tumor-like cells, fibroblasts and mono- nuclear macrophages within the tumor microenvironment. The above results indicated that TSC-RAML exhibited a characteristic and disease-associated plasma proteomic profile. The unique microenvironment, made up of fibroblasts and mono-macrophages, may promote tumorigenesis and TSC-RAML progression. © 2022 Spandidos Publications. All rights reserved.

Item Type:
Journal Article
Journal or Publication Title:
International Journal of Oncology
Additional Information:
Export Date: 2 November 2022
Subjects:
ID Code:
178556
Deposited By:
Deposited On:
04 Nov 2022 14:10
Refereed?:
Yes
Published?:
Published
Last Modified:
22 Nov 2022 12:01