ArticleJournal of translational medicine2013
A three-gene signature as potential predictive biomarker for irinotecan sensitivity in gastric cancer.
Article in Journal of translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- MAVERICC, a Randomized, Biomarker-stratified, Phase II Study of mFOLFOX6-Bevacizumab versus FOLFIRI-Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- The diverse repertoire of ISG15: more intricate than initially thought.Experimental & molecular medicine · 2022Review
- ISG15 and ISGylation in Human Diseases.Cells · 2022Review
- Review
- Interferon-stimulated gene 15 accelerates replication fork progression inducing chromosomal breakage.The Journal of cell biology · 2020Article
- ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression.Cell death & disease · 2020Article
- Gastric Cancer with Radiographically Occult Metastatic Disease: Biology, Challenges, and Diagnostic Approaches.Cancers · 2020Review
- A 21‑gene Support Vector Machine classifier and a 10‑gene risk score system constructed for patients with gastric cancer.Molecular medicine reports · 2020Article
- Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer.Oncology letters · 2017Article
- Prognostic value of a 25-gene assay in patients with gastric cancer after curative resection.Scientific reports · 2017Article
- Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment.Oncotarget · 2017Review
- Plasma mRNA as liquid biopsy predicts chemo-sensitivity in advanced gastric cancer patients.Journal of Cancer · 2017Article
- ISG15 in the tumorigenesis and treatment of cancer: An emerging role in malignancies of the digestive system.Oncotarget · 2016Review
- Article
- Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines.BMC cancer · 2016Article
- RNA-seq reveals determinants for irinotecan sensitivity/resistance in colorectal cancer cell lines.International journal of clinical and experimental pathology · 2014Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePersonalized chemotherapy based on molecular biomarkers can maximize anticancer efficiency. We aim to investigate predictive biomarkers capable of predicting response to irinotecan-based treatment in gastric cancer.
methodsWe examined gene expression of APTX, BRCA1, ERCC1, ISG15, Topo1 and methylation of SULF2 in formalin-fixed paraffin-embedded gastric cancer tissues from 175 patients and evaluated the association between gene expression levels or methylation status and in vitro sensitivity to irinotecan. We used multiple linear regression analysis to develop a gene-expression model to predict irinotecan sensitivity in gastric cancer and validated this model in vitro and vivo.
resultsGene expression levels of APTX, BRCA1 and ERCC1 were significantly lower in irinotecan-sensitive gastric cancer samples than those irinotecan-resistant samples (P<0.001 for all genes), while ISG15 (P=0.047) and Topo1 (P=0.002) were significantly higher. Based on those genes, a three-gene signature were established, which was calculated as follows: Index =0.488 - 0.020× expression level of APTX + 0.015× expression level of Topo1 - 0.011 × expression level of BRCA1. The three-gene signature was significantly associated with irinotecan sensitivity (rho=0.71, P<0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity based on the three-gene signature reached 73% and 86%, respectively. In another independent testing set, the irinotecan inhibition rates in gastric samples with sensitive-signature were much higher than those with resistant-signature (65% vs. 22%, P<0.001). Irinotecan therapy with 20 mg/kg per week to immunodeficient mice carrying xenografts with sensitive-signature dramatically arrested the growth of tumors (P<0.001), but had no effect on mice carrying xenografts with resistant-signature.
conclusionsThe three-gene signature established herein is a potential predictive biomarker for irinotecan sensitivity in gastric cancer.
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