Blood-based Biomarker Assay Research Articles

Expression of MALAT1 in the peripheral whole blood of patients with lung cancer.

A blood-based biomarker assay is a non-invasive way to screen that can identify lung cancer at an earlier stage to improve the clinical outcome. MALAT1 is a broadly expressed, long non-coding RNA in human tissues and is overexpressed in numerous human carcinomas. The potential of MALAT1 in the whole blood of lung cancer was evaluated. In the present study, blood samples of patients with lung cancer and healthy volunteers (controls) were recruited and analyzed by quantitative polymerase chain reaction (qPCR) for MALAT1 expression and clinicopathological data. Lung cancer tissues were also analyzed by qPCR. The expression of MALAT1 in the whole blood of lung cancer was lower compared to the control. The area under the receiver operator curve was 0.718 (P<0.001). Relatively, the expression of MALAT1 was stronger in the whole blood of lung cancer with metastasis compared to non-metastasis. Additionally, the whole blood with bone or brain metastasis exhibited a higher expression of MALAT1 compared to the blood with lymph node or pleura metastasis. Subsequently, a lower expression of MALAT1 was detected in metastatic lymph node tissues than that of the carcinoma in situ of the lung. Taken together, these results indicate that MALAT1 as a biomarker to screen lung cancer may represent a host response to lung cancer.

Emerging blood-based biomarkers for detection of gastric cancer.

Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality, and for improving the management of patients with gastric cancer (GC). Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for population-wide or risk group-based screening programs, while circulating biomarkers that reflect the genetic make-up and dynamics of the tumor would allow monitoring of treatment efficacy, predict recurrences and assess the genetic heterogeneity of the tumor. Recent research to identify blood-based biomarkers of GC has resulted in the identification of a wide variety of cancer-associated molecules, including various proteins, autoantibodies against tumor associated antigens, cell-free DNA fragments, mRNAs and various non-coding RNAs, circulating tumor cells and cancer-derived extracellular vesicles. Each type of these biomarkers provides different information on the disease status, has different advantages and disadvantages, and distinct clinical usefulness. In the current review, we summarize the recent developments in blood-based GC biomarker discovery, discuss the origin of various types of biomarkers and their clinical usefulness and the technological challenges in the development of biomarker assays for clinical use.

THU0128 Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of BI 638683, A Novel CCR1 Antagonist

BackgroundMonocytes and macrophages play a major role in the pathogenesis of rheumatoid arthritis (RA). The chemokine receptor CCR1 regulates migration of these cells to synovial tissue and the bone. It...

Mathematical Model Identifies Blood Biomarker–Based Early Cancer Detection Strategies and Limitations

Most clinical blood biomarkers lack the necessary sensitivity and specificity to reliably detect cancer at an early stage, when it is best treatable. It is not yet clear how early a clinical blood assay can be used to detect cancer or how biomarker-based strategies can be improved to enable earlier detection of smaller tumors. To address these issues, we developed a mathematical model describing dynamic plasma biomarker kinetics in relation to the growth of a tumor, beginning with a single cancer cell. To exemplify a realistic scenario in which biomarker is shed by both cancerous and noncancerous cells, we primed the model on ovarian tumor growth and CA125 shedding data, for which tumor growth parameters and shedding rates are readily available in published literature. We found that a tumor could grow unnoticed for more than 10.1 years and reach a volume of about π/6(25.36 mm)(3), corresponding to a spherical diameter of about 25.36 mm, before becoming detectable by current clinical blood assays. Model parameters were perturbed over log orders of magnitude to quantify ideal shedding rates and identify other blood-based strategies required for early submillimeter tumor detectability. The detection times we estimated are consistent with recently published tumor progression time lines based on clinical genomic sequencing data for several cancers. Here, we rigorously showed that shedding rates of current clinical blood biomarkers are likely 10(4)-fold too low to enable detection of a developing tumor within the first decade of tumor growth. The model presented here can be extended to virtually any solid cancer and associated biomarkers.

MicroRNAs in Plasma of Pancreatic Ductal Adenocarcinoma Patients as Novel Blood-Based Biomarkers of Disease

Development of minimally invasive biomarker assays for early detection and effective clinical management of pancreatic cancer is urgently needed to reduce high morbidity and mortality associated with this malignancy. We hypothesized that if aberrantly expressing microRNAs (miRNA) in pancreatic adenocarcinoma tissues are detected in blood plasma, then plasma profiling of these miRNAs might serve as a minimally invasive early detection biomarker assay for this malignancy. By using a modified protocol to isolate and quantify plasma miRNAs from heparin-treated blood, we show that miRNA profiling in plasma can differentiate pancreatic adenocarcinoma patients from healthy controls. We have profiled four miRNAs, miR-21, miR-210, miR-155, and miR-196a, all implicated in the development of pancreatic cancer with either proven or predicted target genes involved in critical cancer-associated cellular pathways. Of these, miR-155 has recently been identified as a candidate biomarker of early pancreatic neoplasia, whereas elevated expression of miR196a has been shown to parallel progression of disease. The results revealed a sensitivity of 64% and a specificity of 89% with the analyses of plasma levels for this panel of four miRNAs. The area under the receiver operating characteristic curve were estimated at 0.82 and 0.78 without and with leave-one-out cross-validation scheme, respectively. These observations, although a "proof of principle" finding at this time, show the feasibility of developing plasma miRNA profiling as a sensitive and specific blood-based biomarker assay for pancreatic cancer that has the potential of translation to the clinic with additional improvements in the future.