Free circulating mRNA in plasma from breast cancer patients and clinical outcome.
ABSTRACT We studied by real-time PCR cyclin D1 and thymidylate synthase (TS) mRNA in plasma as possible markers of clinical outcome in breast cancer. We observed poor outcome in patients with presence of cyclin D1 mRNA in good-prognosis groups, such as negative vascular invasion. Presence of both markers was associated with non-response to treatment after relapse. In patients treated with tamoxifen, a trend to significant relation between poor outcome and cyclin D1 mRNA was found. Cyclin D1 mRNA in plasma could identify patients with poor overall survival in good-prognosis groups and patients non-responsive to tamoxifen.
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ABSTRACT: During tumor development, tumor cells release their nucleic acids into the blood circulation. This process occurs by apoptotic and necrotic cell deaths along with active cell secretion, resulting in high levels of circulating DNA, mRNA, and microRNA in the blood of patients with breast cancer. As circulating cell-free tumor nucleic acids may reflect the characteristics of the primary tumor and even of micrometastatic cells, they may be excellent blood biomarkers for screening breast cancer. Assays that allow the repetitive monitoring of patients by using blood samples as liquid biopsy may be efficient in assessing cancer progression in patients whose tumor tissue is not available. This review evaluates the recent data on the potential use of circulating cell-free nucleic acids as biomarkers for breast cancer.Breast cancer research: BCR 09/2013; 15(5):211. DOI:10.1186/bcr3446 · 5.88 Impact Factor
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ABSTRACT: Objective Personalized chemotherapy based on predictive biomarkers can maximize efficacy. However, tumor tissue obtained at the time of initial diagnosis will not reflect genetic alterations observed at the time of disease progression. We have examined whether plasma mRNA levels can be a surrogate for tumor levels in predicting chemosensitivity.Methods In 150 gastric cancer patients, mRNA levels of BRCA1 and TS were assessed in plasma and paired tumor tissue. The Mann-Whitney U-test was used to compare mRNA expression levels between tumor samples exhibiting in vitro sensitivity or resistance to docetaxel and pemetrexed. All statistical tests were two-sided.ResultsThere were significant correlations between plasma and tumor mRNA levels of BRCA1 (rho¿=¿0.696, P¿<¿0.001) and TS (rho¿=¿0.620, P¿<¿0.001). BRCA1 levels in plasma (docetaxel-sensitive: 1.25; docetaxel-resistant: 0.50, P¿<¿0.001) and tumor (docetaxel-sensitive: 8.81; docetaxel-resistant: 4.88, P¿<¿0.001) were positively associated with docetaxel sensitivity. TS levels in plasma (pemetrexed-sensitive: 0.90; pemetrexed-resistant: 1.82, P¿<¿0.001) and tumor (pemetrexed-sensitive: 6.56; pemetrexed-resistant: 16.69, P¿<¿0.001) were negatively associated with pemetrexed sensitivity.Conclusions Plasma mRNA expression levels mirror those in the tumor and may have a promising role as potential predictive biomarkers for chemotherapy.
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ABSTRACT: The purpose of the study is to analyze the relationship between tumor thymidylate synthase (TS) mRNA expression levels and raltitrexed/pemetrexed/5-FU sensitivity. We collected freshly removed colorectal tumor specimens from 50 patients. Chemosensitivities to anticancer drugs were evaluated by histoculture drug response assay. We adopted quantitative reverse transcription polymerase chain reaction for TS mRNA detection and immunohistochemical staining for assessing TS expression in tumor tissues. There is a significant relationship between TS mRNA expression levels and in vitro chemosensitivity of freshly removed colorectal tumor specimens to pemetrexed (P < 0.001)/raltitrexed (P = 0.004)/5-FU (P = 0.007). TS mRNA expression levels can predict pemetrexed and raltitrexed sensitivity in colorectal cancer.Cancer Chemotherapy and Pharmacology 11/2013; DOI:10.1007/s00280-013-2354-z · 2.80 Impact Factor