Abstract:
:High throughput gene expression profiling has showed great promise in providing insight into molecular mechanisms. Metastasis-related mRNAs may potentially enrich genes with the ability to predict cancer recurrence, therefore we attempted to build a recurrence-associated gene signature to improve prognostic prediction of colorectal cancer (CRC). We identified 2848 differentially expressed mRNAs by analyzing CRC tissues with or without metastasis. For the selection of prognostic genes, a LASSO Cox regression model (least absolute shrinkage and selection operator method) was employed. Using this method, a 13-mRNA signature was identified and then validated in two independent Gene Expression Omnibus cohorts. This classifier could successfully discriminate the high-risk patients in discovery cohort [hazard ratio (HR) = 5.27, 95% confidence interval (CI) 2.30-12.08, P < 0.0001). Analysis in two independent cohorts yielded consistent results (GSE14333: HR = 4.55, 95% CI 2.18-9.508, P < 0.0001; GSE33113: HR = 3.26, 95% CI 2.16-9.16, P = 0.0176). Further analysis revealed that the prognostic value of this signature was independent of tumor stage, postoperative chemotherapy and somatic mutation. Receiver operating characteristic (ROC) analysis showed that the area under ROC curve of this signature was 0.8861 and 0.8157 in the discovery and validation cohort, respectively. A nomogram was constructed for clinicians, and did well in the calibration plots. Furthermore, this 13-mRNA signature outperformed other known gene signatures, including oncotypeDX colon cancer assay. Single-sample gene-set enrichment analysis revealed that a group of pathways related to drug resistance, cancer metastasis and stemness were significantly enriched in the high-risk patients. In conclusion, this 13-mRNA signature may be a useful tool for prognostic evaluation and will facilitate personalized management of CRC patients.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Tian X,Zhu X,Yan T,Yu C,Shen C,Hu Y,Hong J,Chen H,Fang JYdoi
10.1002/1878-0261.12117subject
Has Abstractpub_date
2017-11-01 00:00:00pages
1544-1560issue
11eissn
1574-7891issn
1878-0261journal_volume
11pub_type
杂志文章abstract:PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.005
更新日期:2015-04-01 00:00:00
abstract::Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases, however, their role in tumor biology and as a drug target is not clear. In the present study, a stable neurotensin (NT) analog induced intracellular calcium release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer ce...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2009.01.006
更新日期:2009-06-01 00:00:00
abstract::The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/i) embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphoma...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.01.001
更新日期:2010-04-01 00:00:00
abstract::JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the cl...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.06.003
更新日期:2011-10-01 00:00:00
abstract::Medullary thyroid cancer (MTC) is a tumor highly resistant to chemo- and radiotherapy. Drug resistance can be induced by epigenetic changes such as aberrant DNA methylation. To overcome drug resistance, we explored a promising approach based on the use of 5-aza-2'-deoxycytidine (AZA), a demethylating agent, in combina...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12070
更新日期:2017-08-01 00:00:00
abstract::The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by perform...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.11.002
更新日期:2011-02-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.01.005
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients. PATIENTS AND METHODS:Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00
abstract::The concept of polypharmacology involves the interaction of drug molecules with multiple molecular targets. It provides a unique opportunity for the repurposing of already-approved drugs to target key factors involved in human diseases. Herein, we used an in silico target prediction algorithm to investigate the mechan...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12810
更新日期:2020-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12138
更新日期:2017-12-01 00:00:00
abstract::Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylatio...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12785
更新日期:2020-11-01 00:00:00
abstract::Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.007
更新日期:2016-05-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12499
更新日期:2019-07-01 00:00:00
abstract::The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic op...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12433
更新日期:2019-02-01 00:00:00
abstract::Pharmacogenomics is the study of genetic factors determining drug response or toxicity. The use of pharmacogenomics is especially desirable in oncology because the therapeutic index of oncology drugs is often narrow, the need for favorable drug response is often acute, and the consequences of drug toxicity can be life...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2012.01.005
更新日期:2012-04-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12878
更新日期:2020-12-11 00:00:00
abstract::A significant proportion of estrogen receptor-positive (ER+) breast cancer (BC) initially responds to endocrine therapy but eventually evolves into therapy-resistant BC. Transcription factor AP-2 gamma (TFAP2C) is a known regulator of ER activity, and high expression of TFAP2C is associated with a decreased response t...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12871
更新日期:2020-12-02 00:00:00
abstract::In order to secure high-quality cancer care for increasing numbers of cancer patients in the upcoming decades, the complete continuum of cancer research and cancer care needs a thorough overhaul, with more emphasis on prevention and early detection, and a greater focus on the development of innovative treatments that ...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12441
更新日期:2019-03-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12521
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested. METHODS:We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.08.002
更新日期:2011-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12321
更新日期:2018-08-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12536
更新日期:2019-09-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12386
更新日期:2018-12-01 00:00:00
abstract::Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms rema...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12765
更新日期:2020-10-01 00:00:00
abstract::Angiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detec...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.12.017
更新日期:2014-05-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is an important process in embryonic development, fibrosis, and cancer metastasis. During cancer progression, the activation of EMT permits cancer cells to acquire migratory, invasive, and stem-like properties. A growing body of evidence supports the critical link between EMT an...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12096
更新日期:2017-07-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.09.005
更新日期:2010-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12882
更新日期:2020-12-15 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12193
更新日期:2018-05-01 00:00:00