Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Detection of prognostic biomarkers with solid-phase proximity ligation assay in patients with colorectal cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
Show others and affiliations
2016 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 9, no 3, 251-255 p.Article in journal (Refereed) Published
Abstract [en]

Background: In the search for prognostic biomarkers a significant amount of precious biobanked blood samples is needed if conventional analyses are used. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyse many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of  SP-PLA in patients with colorectal cancer (CRC).

Material and methods: Plasma from patients with stage I-IV CRC, with (n=31) and without (n=29) disease dissemination at diagnosis or later, was analysed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5 ml plasma. Carcinoembryonic antigen (CEA), analysed earlier on this cohort, was used as a reference.

Results: A total of 21 of the 35 proteins were detectable with SP-PLA. Patients in stage II-III with disseminated disease had lower plasma concentrations of HCC-4 (p=0.025). Low plasma levels of TIMP-1 were seen in patients with disseminated disease stage II (p=0.003). The level of CEA was higher in patients with disease dissemination compared to those without (p=0.007).

Conclusion: SP-PLA has the ability to analyse many tumour markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information compared with CEA. 

Place, publisher, year, edition, pages
2016. Vol. 9, no 3, 251-255 p.
Keyword [en]
colorectal cancer, biomarkers, SP-PLA, recurrence, prognosis
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-224696DOI: 10.1016/j.tranon.2016.04.001ISI: 000378028300014PubMedID: 27267845OAI: oai:DiVA.org:uu-224696DiVA: diva2:717856
Funder
EU, FP7, Seventh Framework Programme, 294409; 259796
Available from: 2014-05-19 Created: 2014-05-19 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Colorectal Cancer: Aspects of Heredity, Prognosis and Tumour Markers
Open this publication in new window or tab >>Colorectal Cancer: Aspects of Heredity, Prognosis and Tumour Markers
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal cancer (CRC) is one of the most common cancer types and leading causes of cancer death worldwide. Since CRC is a heterogenic disease, there is a demand for increased knowledge of the underlying genetic and epigenetic mechanisms. The aim of this thesis was to investigate heredity and potential tumour markers in relation to prognosis. In paper I, survival of patients with CRC and a positive family history of CRC in first-degree relatives was analysed. Patients with colon cancer and positive family history of CRC had improved survival compared to patients with negative family history. This improvement in survival could not be explained by known clinico-pathological factors. In paper II, we investigated the prognostic value of Tryptophanyl t-RNA synthetase (TrpRS) in tissues from patients operated for CRC. Low protein expression of TrpRS in primary tumour tissues correlated with increased risk of recurrence and poorer survival. In paper III, the prognostic value of microsatellite instability (MSI) and the correlation to heredity for CRC in first-degree relatives was investigated. Patients with proximal colon cancer and MSI had improved cancer specific survival. There were no correlation between MSI and heredity. In paper IV, we evaluated the potential use of proximity ligation assay (SP-PLA) in patients with CRC, by simultaneous analysis of 35 proteins in only 5 μl plasma. SP-PLA is a suitable method for protein detection and might give valuable guidance in pursuing new prognostic and predictive tumour markers. However, none of the markers selected for present SP-PLA analyses gave better prognostic information than CEA. In conclusion, heredity is related to better survival independent of MSI in patients with CRC and MSI is associated with better prognosis in proximal colon cancer. Detection and increased knowledge of molecular mechanism in CRC is important, however it needs to be further investigated and validated in clinical use. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1011
Keyword
colorectal cancer, heredity, Tryptophanyl t-RNA synthetase, microsatellite instability, SP-PLA, prognosis, biomarkers
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-224624 (URN)978-91-554-8975-5 (ISBN)
Public defence
2014-09-06, Grönwallsalen, Akademiska sjukhuset, ingång 70, bv, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2014-06-13 Created: 2014-05-15 Last updated: 2014-07-25

Open Access in DiVA

fulltext(277 kB)205 downloads
File information
File name FULLTEXT01.pdfFile size 277 kBChecksum SHA-512
229d97ba7c20f268d67c2073367a16f3b8da4f8b1df679cb3cc1c3f2b1353caf8cad619eac132a7cebcf06d83ee006b55a0a0d3e3d2497b90ffb83b56a104e0f
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Ghanipour, LanaLandegren, UlfGlimelius, BengtPåhlman, LarsBirgisson, Helgi

Search in DiVA

By author/editor
Ghanipour, LanaLandegren, UlfGlimelius, BengtPåhlman, LarsBirgisson, Helgi
By organisation
Colorectal SurgeryDepartment of Immunology, Genetics and PathologyDepartment of Radiology, Oncology and Radiation ScienceDepartment of Surgical Sciences
In the same journal
Translational Oncology
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 205 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 889 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf