Project description:Introduction: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin. To our knowledge, circulating exosome microRNAs have not been well evaluated as biomarkers for breast cancer diagnosis or monitoring. Methods: Exosomes were collected from the conditioned media of human breast cancer cell lines, mouse plasma of patient-derived orthotopic xenograft models (PDX), and human plasma samples. Exosomes were verified by electron microscopy, nanoparticle tracking analysis, and western blot. Cellular and exosome microRNAs from breast cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome microRNA expression was analyzed by qRT-PCR analysis. Results: Small RNA sequencing and qRT-PCR analysis showed that several microRNAs are selectively encapsulated or highly enriched in breast cancer exosomes. Importantly, the selectively enriched exosome microRNA, human miR-1246, was detected at significantly higher levels in exosomes isolated from PDX mouse plasma, indicating that tumor exosome microRNAs are released into the circulation and can serve as plasma biomarkers for breast cancer. This observation was extended to human plasma samples where miR-1246 and miR-21 were detected at significantly higher levels in the plasma exosomes of 16 breast cancer patients as compared to the plasma exosomes of healthy control subjects. Receiver Operating Characteristic (ROC) curve analysis indicated that the combination of plasma exosome miR-1246 and miR-21 levels is a better indicator of breast cancer than their individual levels. Conclusions: Our results demonstrate that certain microRNA species, such as miR-21 and miR-1246, are selectively enriched in human breast cancer exosomes and significantly elevated in the plasma of breast cancer patients. These findings indicate a potential new strategy to selectively analyze plasma breast cancer microRNAs indicative of the presence of breast cancer.
Project description:Colorectal cancer is the third most common malignancy and the fourth most common cause of cancer mortality worldwide. In 2008, more than one million cases were newly diagnosed, and more than 600,000 people died from the disease. Given its slow development from removable precancerous lesions and curable early stages, screening for CRC has the potential to reduce both the incidence and mortality of the disease. However, compliance with current screening methods remains poor and there is a clear need for an accurate in vitro blood test to increase participation in colorectal cancer screening. In this study, we performed genome-wide gene expression profiling of peripheral blood samples from 100 healthy controls and 100 colorectal cancer patients using PAXgeneTM technology and Affymetrix GeneChip® microarrays. We show that monitoring gene expression in blood results in distinct transcriptional profiles between the controls and cancer patients. Thus, the microarray-based blood gene expression profiling holds great promise for developing novel biomarkers for colorectal cancer detection.
Project description:Recent advances in high-throughput technologies have provided an unprecedented opportunity to identify molecular markers of disease processes. This plethora of complex -omics data has simultaneously complicated the problem of extracting meaningful molecular signatures and opened up new opportunities for more sophisticated integrative and holistic approaches. In this era, effective integration of data-driven and knowledge-based approaches for biomarker identification has been recognised as key to improving the identification of high-performance biomarkers, and necessary for translational applications. Here, we have evaluated the role of circulating microRNA as a means of predicting the prognosis of patients with colorectal cancer, which is the second leading cause of cancer-related death worldwide. We have developed an innovative multi-objective optimisation method which effectively integrates a data-driven approach with the knowledge obtained from the microRNA-mediated regulatory network to identify robust plasma microRNA signatures which are reliable in terms of predictive power as well as functional relevance. We have found 9 signatures of colorectal cancer prognosis comprising a total of 19 circulating microRNAs. The identified signatures predict the patients’ survival outcome and target pathways underlying colorectal cancer progression. The altered expression of the microRNAs within these signatures was confirmed in two independent public datasets of plasma and tumour samples of patients in early stage versus advanced colorectal cancer.
Project description:To investigate miRNA expression profiles between gastric cancers plasma and healthy controls plasma,screening the microRNAs that can serve as plasma biomarkers for the early diagnosis of gastric cancer by miRNA array.
Project description:Colorectal cancer remains the leading cause of cancer death worldwide. The 5-year annual survival is less than half of the incidence rate that is predominantly due to late diagnosis of the disease striking the very urgent clinical necessity for biomarkers capable of detecting cancer malignancy at an early onset. During neoplastic transformation, cells undergo several behavioral changes that subsequently result in defects in cell division, immune tolerance, inflammation, and cellular death mechanisms. These processes lead to the development of tumor antigens (TA) that evoke an immune response and subsequent generation of antibodies against self-proteins, called autoantibodies (AAbs). This study aims to identify autoantibody biomarkers in patient’s sera for early screening of the cancer. High-density human proteome array having approximately 17,000 full-length recombinant human proteins were used in the study. The generation of an autoimmune response against important cancer-linked pathways could be important in terms of screening for the disease. The process of immune surveillance starts as tumorigenesis begins and hence autoantibodies can be detected in a very early stage of cancer. Moreover, AAbs can be easily extracted from blood serum through the least invasive test for disease screening.
Project description:MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNAs whose dysregulation of expression plays an important role in cancer development. Circulating miRNAs are novel biomarkers in several cancers. Thus, we explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma (MM) patients. The expression levels of four miRNAs in plasma were upregulated while eight miRNAs were downregulated in MM patients compared with healthy controls according to microarray. MiRNA microarray was conducted to determine deregulated miRNAs in plasma of 9 MM patients and 7 healthy controls.
Project description:MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNAs whose dysregulation of expression plays an important role in cancer development. Circulating miRNAs are novel biomarkers in several cancers. Thus, we explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma (MM) patients. The expression levels of four miRNAs in plasma were upregulated while eight miRNAs were downregulated in MM patients compared with healthy controls according to microarray.
Project description:Background. Radioiodide 131I is commonly used to treat thyroid cancer and hyperthyroidism, and 131I releases during nuclear accidents have resulted in increased incidence of thyroid cancer in children. To develop a better understanding of underlying cellular mechanisms behind 131I exposure and identify potential biomarkers, the aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats. Materials and methods. Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1–1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression patterns in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). Results. Nine 131I exposure-related biomarkers (Afp and RT1-Bb,ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Four dose-related biomarker candidates (APRT, LDHA) and (TGM3 and DSG4) were identified in thyroid and plasma, respectively. Candidate biomarkers for thyroid function were the upstream regulator PPARG and the proteins ACADL and SORBS2 (all activities), TPO and TG (low activities)). 131I exposure was shown to have a profound effect on metabolism, the immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated. Conclusion. Exposure-related and dose-related effects on gene and protein expression were observed, thereby identifying several candidate genes that could be used as potential biomarkers for exposure, absorbed dose and thyroid function.
Project description:By comparing urinary microRNA expression in representative cases of pancreatic and gastric cancer with that in healthy individuals, we were able to extract candidate biomarkers.
Project description:The study was conducted as the marker discovery phase to identify potential microRNA (miRNA) candidates for colorectal cancer (CRC) screening. Genome-wide profiling with next-generation sequencing (NGS) was performed using plasma samples from 20 newly diagnosed CRC cases and 20 controls free of colorectal neoplasms matched by age and sex.