liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer
Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
Oslo University Hospital, Norway; Oslo University Hospital, Norway.
Oslo University Hospital, Norway; University of Oslo, Norway; University of Oxford, England.
Show others and affiliations
2015 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, no 16, 3759-3770 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 50 UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical highrisk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (greater than 75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (C) 2015 AACR.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH , 2015. Vol. 21, no 16, 3759-3770 p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-122121DOI: 10.1158/1078-0432.CCR-14-3294ISI: 000361909100024PubMedID: 25910952OAI: diva2:861769

Funding Agencies|Norwegian Cancer Society [PR-2006-0442, PR-2007-0166]; South-Eastern Norway Regional Health Authority

Available from: 2015-10-19 Created: 2015-10-19 Last updated: 2015-12-02

Open Access in DiVA

fulltext(446 kB)7 downloads
File information
File name FULLTEXT01.pdfFile size 446 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Sun, Xiao-Feng
By organisation
Division of Clinical SciencesFaculty of Medicine and Health SciencesDepartment of Oncology
In the same journal
Clinical Cancer Research
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 7 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

Altmetric score

Total: 69 hits
ReferencesLink to record
Permanent link

Direct link