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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - A multi-omics study of diagnostic markers and the unique inflammatory tumor micro-environment involved in tuberous sclerosis complex-related renal angiomyolipoma
AU - Wang, Zhan
AU - Xiaoyan, L.
AU - Wenda, W.
AU - Jing, W.
AU - Seery, S.
AU - Jiyu, X.
AU - Haidan, S.
AU - Yuncui, Y.
AU - Yang, Z.
AU - Xu, W.
AU - Zhangcheng, L.
AU - Yanan, L.
AU - Wei, S.
AU - Lulu, J.
AU - Yushi, Z.
N1 - Export Date: 2 November 2022
PY - 2022/9/15
Y1 - 2022/9/15
N2 - 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.
AB - 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.
KW - diagnostic markers
KW - proteomics
KW - RNA transcriptome
KW - tuberous sclerosis complex
KW - tumor microenvironment
KW - UPLC-MS
U2 - 10.3892/ijo.2022.5422
DO - 10.3892/ijo.2022.5422
M3 - Journal article
VL - 61
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 5
M1 - 132
ER -