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Updated: Mar 31, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Differential Protein Expression in Small Intestinal Neuroendocrine Tumors and Liver Metastases
Michelle Kang Kim1, Fei Ye, Daguang Wang
1From the Departments of *Medicine/Gastroenterology and †Pathology, Mount Sinai School of Medicine; ‡Liver Cancer Program, Hofstra-North Shore Long Island Jewish School of Medicine; §Department of Surgery/Division of Surgical Oncology, Mount Sinai School of Medicine; and ∥Mount Sinai Liver Cancer Program, Mount Sinai Hospital, New York, NY.
Objective:
Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients.
Methods:
Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry.
Results:
Comparing primary SI-NETs with matched normal small-bowel mucosa, 9 proteins were upregulated and cyclin E was downregulated. The SI-NET liver metastases demonstrated upregulation of P-ERK and p27 but downregulation of CDK2 and CDC25B. When comparing primary SI-NET with their paired liver metastases, cyclin E demonstrated a significant upregulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SI-NETs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver.
Conclusions:
Few studies have compared protein expression in paired primary and metastatic SI-NETs. Our findings reveal changes in a limited number of proteins, suggesting that these may be targets for therapy.
Insights
Small intestinal neuroendocrine tumors (SI-NETs) often spread to the liver. This study identified key protein changes in SI-NET metastasis, revealing potential therapeutic targets for this rare cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Small intestinal neuroendocrine tumors (SI-NETs) are frequently diagnosed at advanced metastatic stages.
- Understanding the molecular mechanisms of SI-NET metastasis is crucial for developing effective treatments.
Purpose of the Study:
- To identify protein expression differences between primary SI-NETs and their matched liver metastases.
- To discover novel protein biomarkers and therapeutic targets for SI-NET metastasis.
Main Methods:
- Proteomic analysis using a novel protein array on paired primary SI-NETs and liver metastases from 25 patients.
- Multiplex immunoblotting with 136 antibodies and Significant Analysis of Microarray (SAM).
- Immunohistochemistry on tissue microarrays from 27 archived specimens.
Main Results:
- Compared to normal tissue, 9 proteins were upregulated and cyclin E downregulated in primary SI-NETs.
- SI-NET liver metastases showed upregulation of P-ERK and p27, and downregulation of CDK2 and CDC25B.
- Cyclin E was significantly upregulated in liver metastases compared to primary SI-NETs; p38 and p27 were higher, while Cdc25b was lower in metastases.
Conclusions:
- This study provides novel insights into protein expression changes during SI-NET metastasis.
- Identified specific proteins (e.g., cyclin E, p27, Cdc25b) that are differentially expressed in primary versus metastatic SI-NETs.
- These proteins represent potential therapeutic targets for managing SI-NET metastasis.
