ArticleMolecular oncology2013
Topoisomerase 1(TOP1) gene copy number in stage III colorectal cancer patients and its relation to prognosis.
Article in Molecular oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.PloS one · 2014Trial
- Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer.BMC cancer · 2017Article
- Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA DamageFrontiers in pharmacology · 2017Article
- Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan-Meier plotter.PloS one · 2017Article
- Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer.Journal of ovarian research · 2016Article
- Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair-proficient colorectal cancers.Molecular oncology · 2015Article
- Measuring ERCC1 protein expression in cancer specimens: validation of a novel antibody.Scientific reports · 2014Article
- Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development.Frontiers in oncology · 2013Review
- An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort.BMC cancer · 2013Article
- Topoisomerase 1(TOP1) gene copy number in stage III colorectal cancer patients and its relation to prognosis.Molecular oncology · 2013Article
- Mechanisms of topoisomerase I (TOP1) gene copy number increase in a stage III colorectal cancer patient cohort.PloS one · 2013Article
- Genome wide analysis of chromosomal alterations in oral squamous cell carcinomas revealed over expression of MGAM and ADAM9.PloS one · 2013Article
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10 authors.
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Abstract
purposeA Topoisomerase 1 (Top1) poison is frequently included in the treatment regimens for metastatic colorectal cancer (mCRC). However, no predictive biomarkers for Top1 poisons are available. We here report a study on the TOP1 gene copy number in CRC patients and its association with patient prognosis and tumor cell proliferation. EXPERIMENTAL
designThe study included TOP1 and CEN-20 fluorescence in situ hybridization (FISH) analyses on formalin fixed paraffin embedded (FFPE) tissue sections from 154 stage III CRC chemonaïve patients. The frequencies of aberration in the TOP1 gene copy number, the CEN-20 copy number and the TOP1/CEN-20 ratio were analyzed and associated with overall survival (OS), time to recurrence (TTR) and in a subgroup analysis of rectal cancer patients only with time to local recurrence (LR in RC). Moreover, the TOP1 and CEN-20 copy numbers were correlated with the tumor Ki67 proliferation index.
results35.7% of the tumors had an increased TOP1 copy number above 4n gene copies per cell and 28.6% and 9.7% had a TOP1/CEN-20 ratio ≥1.5 or ≥2.0, respectively. The TOP1 copy number and the TOP1/CEN-20 ratios were separately added into multivariate analyses as continuous variables, in which also age, gender, primary tumor location and Ki67 status were added as covariates. In contrast to the TOP1/CEN-20 ratio, the TOP1 copy number was significantly associated with OS (HR: 0.62; 95% CI: 0.42-0.90; p = 0.01). Neither the TOP1 copy number nor the ratio was significantly associated with TTR and only the TOP1/CEN-20 ratio was significantly associated with LR in RC (HR: 0.25; 95% CI: 0.08-0.83; p = 0.02). No significant correlation was found between the TOP1 copy number and proliferation, while a weak and inverse correlation between the CEN-20 copy number and proliferation was observed.
conclusionsThis study showed that increased TOP1 gene copy numbers are frequent findings in cancer cells in stage III CRC tumors but unrelated to the proliferative status of the tumors. The association with prognosis is important to consider when planning and analyzing future studies investigating TOP1 as a potential predictive biomarker for Top1 poisons.
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