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Updated: Aug 6, 2025
A Streamlined Approach for Mass Spectrometry-Based Proteomics Using Selected Tissue Regions
Published on: April 18, 2025
Proteomic analysis of small intestinal neuroendocrine tumors and mesenteric fibrosis
Anela Blažević1, Anand M Iyer1, Marie-Louise F van Velthuysen2
1Department of Internal Medicine, Section Endocrinology, Erasmus University Medical Center and Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Abstract:
Mesenteric metastases in small intestinal neuroendocrine tumors (SI-NETs) are associated with mesenteric fibrosis (MF) in a proportion of patients. MF can induce severe abdominal complications, and an effective preventive treatment is lacking. To elucidate possible novel therapeutic targets, we performed a proteomics-based analysis of MF. The tumor cell and stromal compartment of primary tumors and paired mesenteric metastases of SI-NET patients with MF (n = 6) and without MF (n = 6) was analyzed by liquid chromatography-mass spectrometry-based proteomics. Analysis of differential protein abundance was performed. Collagen alpha-1(XII) (COL12A1) and complement component C9 (C9) expression was evaluated by immunohistochemistry (IHC) in mesenteric metastases. A total of 2988 proteins were identified. Unsupervised hierarchical clustering showed close clustering of paired primary and mesenteric tumor cell samples. Comparing MF to non-MF samples, we detected differentially protein abundance solely in the mesenteric metastasis stroma group. There was no differential abundance of proteins in tumor cell samples or primary tumor stroma samples. Analysis of the differentially abundant proteins (n = 36) revealed higher abundance in MF samples of C9, various collagens and proteoglycans associated with profibrotic extracellular matrix dysregulation and signaling pathways. Proteins involved in fatty acid oxidation showed a lower abundance. COL12A1 and C9 were confirmed by IHC to have significantly higher expression in MF mesenteric metastases compared to non-MF. In conclusion, proteome profiles of SI-NETs with and without MF differ primarily in the stromal compartment of mesenteric metastases. Analysis of differentially abundant proteins revealed possible new signaling pathways involved in MF development. In conclusion, proteome profiles of SI-NETs with and without MF differ primarily in the stromal compartment of mesenteric metastases. Analysis of differentially abundant proteins revealed possible new signaling pathways involved in MF development.
Insights
Mesenteric fibrosis in small intestinal neuroendocrine tumors (SI-NETs) involves altered stromal proteins, including elevated Collagen alpha-1(XII) and complement component C9, suggesting new therapeutic targets for this condition.
Area of Science:
- Oncology
- Proteomics
- Gastroenterology
Background:
- Mesenteric fibrosis (MF) complicates small intestinal neuroendocrine tumors (SI-NETs), leading to severe abdominal issues.
- Current treatments for MF are lacking, necessitating research into novel therapeutic targets.
Purpose of the Study:
- To identify potential therapeutic targets for MF in SI-NETs by analyzing protein expression differences.
- To compare the proteomic profiles of mesenteric metastases with and without MF.
Main Methods:
- Liquid chromatography-mass spectrometry-based proteomics was used to analyze tumor and stromal compartments of mesenteric metastases from SI-NET patients.
- Immunohistochemistry (IHC) was employed to validate the expression of specific proteins, Collagen alpha-1(XII) (COL12A1) and complement component C9 (C9).
Main Results:
- Proteomic analysis identified 2988 proteins, with significant differences found exclusively in the stromal compartment of mesenteric metastases between MF and non-MF groups.
- Higher abundance of C9, collagens, and proteoglycans associated with profibrotic pathways was observed in MF samples.
- Lower abundance of proteins involved in fatty acid oxidation was noted in MF samples.
- IHC confirmed significantly higher expression of COL12A1 and C9 in MF mesenteric metastases.
Conclusions:
- The proteomic profiles of SI-NETs with and without MF are distinct, primarily within the stromal compartment of mesenteric metastases.
- The identified differentially abundant proteins and pathways offer potential novel therapeutic targets for preventing or treating MF in SI-NET patients.
