In situ proteomic analysis by MALDI imaging identifies ubiquitin and thymosin-β4 as markers of malignant intraductal pancreatic mucinous neoplasms.
Rebours. Vinciane V; Le Faouder. Julie J; Laouirem. Samira S; Mebarki. Mounya M; Albuquerque. Miguel M; Camadro. Jean-Michel JM; Léger. Thibaut T; Ruszniewski. Philippe P; Lévy. Philippe P; Paradis. Valérie V; Bedossa. Pierre P; Couvelard. Anne A
Key Findings
- Ubiquitin and an acetylated fragment of thymosin‑beta‑4 (amino acids 2‑42) are over‑expressed in high‑grade intraductal pancreatic mucinous neoplasms (IPMN).
- MALDI imaging identified these proteins as the most discriminating peaks between low‑ and high‑grade IPMN samples.
- Immunohistochemistry on tissue microarrays and fine‑needle aspiration samples confirmed the association, supporting their use as diagnostic markers.
Practical Outcomes
- For biohackers, the findings mainly point to a potential diagnostic tool for aggressive pancreatic cysts, not a therapeutic or performance‑enhancing application. There is no actionable protocol for supplementing or modulating thymosin‑beta‑4 based on this study.
Summary
Researchers used a special imaging technique to look at proteins in early pancreatic tumors and found that both ubiquitin and a piece of the protein thymosin‑beta‑4 are higher in the more dangerous forms. This suggests they could be used as markers to decide if surgery is needed, but the study does not give any advice on using these peptides for health or performance.
Abstract
Intraductal pancreatic mucinous neoplasms (IPMN) are precancerous cystic lesions. The aim was to investigate the in situ IPMN proteome using MALDI (Matrix-Assisted Laser Desorption/Ionisation) imaging and to characterize biomarkers associated with the grade of dysplasia. Frozen human Branch duct -IPMN sections were selected according to dysplasia and proteomic analyses were performed by MALDI imaging to obtain mass spectra distribution. The most discriminating peaks were identified using tissue extraction and nanoLC-ESI-MS/MS. Identified peaks were validated in independent series of IPMN by immunochemistry on surgical specimens (tissue-microarrays (TMA), n = 45) and endoscopic ultrasound fine-needle aspiration (EUS FNA) samples (n = 25). BD-IPMN samples with low (n = 10) and high (n = 10) grades of dysplasia were analyzed. Differential spectra of proteins were found in the two groups with significantly different intensities (n = 15). The two peaks (intense in high grade IPMN) (m/z 8565 and 4747) were characterized as the monomeric ubiquitin (Mascot score = 319.22) and an acetylated fragment of thymosin-β4 (2-42) (Omssa score = 1.37 E-9). Validation on TMA and EUS FNA samples confirmed that ubiquitin was overexpressed in high grade dysplasia (p = 0.04 and p = 0.0004). Thymosin-β4 expression was confirmed on TMA by immunohistochemistry on high grade IPMN (p = 0.011). Ubiquitin and thymosin-β4 are overexpressed in IPMN with high grade dysplasia. Positive immunochemical staining on EUS-FNA material is a major argument in support of preventive resection.
Study Information
pubmed
2013
2013-12-17T00:00:00.000Z
10.1016/j.pan.2013.12.001
24
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