Translational Medicine Communications
Label-free serum proteomics and multivariate data analysis identifies biomarkers and expression trends that differentiate Intraductal papillary mucinous neoplasia from pancreatic adenocarcinoma and healthy controls
- Mayank Saraswat†,
- Heini Nieminen†,
- Sakari Joenvaara,
- Tiialotta Tohmola,
- Hanna Seppänen,
- Ari Ristimäki,
- Caj Haglund† and
- Risto Renkonen†
†Contributed equally
Translational Medicine Communications20194:6
© The Author(s) 2019
- Received: 25 February 2019
- Accepted: 25 April 2019
- Published: 14 May 2019
Abstract
Background
Intraductal Papillary Mucinous Neoplasia (IPMN) are potentially malignant cystic tumors of the pancreas. IPMN can progress from low to moderate to high grade dysplasia and further to IPMN associated carcinoma. Often the difference between benign and malignant nature of the IPMN is not clear preoperatively. We aim to elucidate molecular expression patterns of various grades of IPMN and pancreatic carcinoma. Additionally we suggest potential novel biomarkers to differentiate IPMN from healthy individuals and pancreatic carcinoma to enable early detection as well as help in differential diagnosis in future.
Methods
We have performed retrospective label-free proteomic analysis of the serum samples from 44 patients with various grades of benign IPMN or IPMN associated carcinoma and 11 healthy controls. Proteomic data was further analyzed by various multivariate statistical methods. Four groups of samples (low-grade, high-grade IPMN, pancreatic carcinoma and age- and sex-matched healthy controls) were compared with ANOVA. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) modeling gave S-plot for feature selection. Stringently selected potential markers were further evaluated with ROC curve analysis and area under the curve was calculated. Differentially expressed proteins were used for pathway analysis. Linear trend analysis (Mann Kendall test) was used for identifying significant increasing or decreasing trends from healthy-low grade-high grade IPMN-pancreatic carcinoma.
Results
Based on protein expression (436 proteins quantified), PCA separated most sample groups from each other. S-Plot selected biomarker panels with moderate to very high AUC values for differentiating controls from Low-, High-Grade IPMN and carcinoma. Linear trend analysis identified 12 proteins which were consistently increasing or decreasing trend among the groups. We found potential biomarkers to differentiate healthy controls from different degrees of dysplasia and pancreatic carcinoma. These biomarkers can classify IPMN, carcinoma and healthy controls from each other which is an unmet clinical need. Data are available via ProteomeXchange with identifier PXD009139.
Conclusion
Kininogen-1 was able to differentiate healthy persons from low and high-grade IPMN. Retinol binding protein-4 could classify the low-grade IPMN from pancreatic carcinoma. Twelve proteins including apolipoproteins and complement proteins had significantly increasing or decreasing trends from healthy to low to high-grade IPMN to pancreatic carcinoma.
Keywords
- IPMN
- Low-grade dysplasia
- Pancreatic carcinoma
- Serum proteomics
- UDMSE
No comments:
Post a Comment