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      MicroRNA Expression Characterizes Oligometastasis(es)

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          Abstract

          Background

          Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.

          Methods

          Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.

          Results

          Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.

          Conclusions

          These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.

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          Most cited references42

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          Oligometastases.

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            Oligometastases revisited.

            We previously proposed a clinical state of metastasis termed 'oligometastases' that refers to restricted tumor metastatic capacity. The implication of this concept is that local cancer treatments are curative in a proportion of patients with metastases. Here we review clinical and laboratory data that support the hypothesis that oligometastasis is a distinct clinical entity. Investigations of the prevalence, mechanism of occurrence, and position in the metastatic cascade, as well as the determination of molecular markers to distinguish oligometastatic from polymetastatic disease, are ongoing.
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              Actual 10-year survival after resection of colorectal liver metastases defines cure.

              Resection of colorectal liver metastases (CLM) in selected patients has evolved as the standard of care during the last 20 years. In the absence of prospective randomized clinical trials, a survival benefit has been deduced relative to historical controls based on actuarial data. There is now sufficient follow-up on a significant number of patients to address the curative intent of resecting CLM. Retrospective review of a prospectively maintained database was performed on patients who underwent resection of CLM from 1985 to 1994. Postoperative deaths were excluded. Disease-specific survival (DSS) was calculated from the time of hepatectomy using the Kaplan-Meier method. There were 612 consecutive patients identified with 10-year follow-up. Median DSS was 44 months. There were 102 actual 10-year survivors. Ninety-nine (97%) of the 102 were disease free at last follow-up. Only one patient experienced a disease-specific death after 10 years of survival. In contrast, 34% of the 5-year survivors suffered a cancer-related death. Previously identified poor prognostic factors found among the 102 actual 10-year survivors included 7% synchronous disease, 36% disease-free interval less than 12 months, 25% bilobar metastases, 50% node-positive primary, 39% more than one metastasis, and 35% tumor size more than 5 cm. Patients who survive 10 years appear to be cured of their disease, whereas approximately one third of actual 5-year survivors succumb to a cancer-related death. In well-selected patients, there is at least a one in six chance of cure after hepatectomy for CLM. The presence of poor prognostic factors does not preclude the possibility of long-term survival and cure.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                13 December 2011
                : 6
                : 12
                : e28650
                Affiliations
                [1 ]Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, United States of America
                [2 ]Ludwig Center for Metastasis Research, University of Chicago, Chicago, Illinois, United States of America
                [3 ]Department of Medicine Center for Biomedical Informatics, University of Chicago, Chicago, Illinois, United States of America
                [4 ]Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, United States of America
                [5 ]Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois, United States of America
                [6 ]Department of Pathology Committee on Cancer Biology, University of Chicago, Chicago, Illinois, United States of America
                [7 ]Department of Surgery, University of Chicago, Chicago, Illinois, United States of America
                [8 ]Department of Radiation Oncology Duke University Medical Center, Durham, North Carolina, United States of America
                Roswell Park Cancer Institute, United States of America
                Author notes

                Conceived and designed the experiments: YAL HRX RRW SH. Performed the experiments: NNK QZ TED HF SP MF SAK. Analyzed the data: YAL JKS NNK HRX YH MDH QZ RM TED HF XY YL SJC RRW SAK KC. Contributed reagents/materials/analysis tools: YAL HRX YH QZ XY MCP. Wrote the paper: YAL NNK HRX MDH QZ XY RRW SAK SJC.

                Article
                PONE-D-11-19940
                10.1371/journal.pone.0028650
                3236765
                22174856
                e7483841-1071-4c71-8be1-44169eb188cb
                Lussier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 10 October 2011
                : 11 November 2011
                Page count
                Pages: 14
                Categories
                Research Article
                Biology
                Computational Biology
                Molecular Genetics
                Gene Expression
                Microarrays
                Genomics
                Genome Analysis Tools
                Transcriptomes
                Genome Databases
                Sequence Databases
                Functional Genomics
                Genome Expression Analysis
                Model Organisms
                Animal Models
                Mouse
                Medicine
                Oncology
                Basic Cancer Research
                Metastasis
                Cancer Treatment
                Clinical Trials (Cancer Treatment)
                Radiation Therapy
                Radiotherapy

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                Uncategorized

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