Search: onr:"swepub:oai:lup.lub.lu.se:8b17b2c1-c020-475a-8c4d-c3774e376d1d" >
Mass spectrometry-b...
Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker
-
- Byrling, Johannes (author)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,Skåne University Hospital
-
- Kristl, Theresa (author)
- Lund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
- Hu, Dingyuan (author)
- Lund University,Lunds universitet,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,Skåne University Hospital
-
show more...
-
- Pla, Indira (author)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups
-
- Sanchez, Aniel (author)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups
-
- Sasor, Agata (author)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
-
- Andersson, Roland (author)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,Skåne University Hospital
-
- Marko-Varga, György (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups
-
- Andersson, Bodil (author)
- Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
-
show less...
-
(creator_code:org_t)
- 2020-09-04
- 2020
- English.
-
In: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 18:1
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://translationa...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- Biliary tract cancer
- Biomarker
- Distal cholangiocarcinoma
- Mass spectrometry
- Parallel reaction monitoring
- Stroma
- Thrombospondin-2
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database