Serum-based Biomarkers Research Articles

An integrated cross-species approach for the discovery of serum-based diagnostic biomarkers of PDAC using a genetically engineered murine model (GEMM).

218 Background: The development of sensitive and specific biomarkers for the early diagnosis of human pancreatic ductal adenocarcinoma (PDAC) represents a major unmet clinical need. GEMMs that faithfully recapitulate the clinical, histological and molecular features of PDAC and capture its genomic complexity (including that triggered by a truncating germline Brca2 mutation) coupled with state of the art proteomic technologies can overcome some of the challenges associated with the analysis of a heterogeneous human disease. We have conducted a large scale screen for differentially expressed glycoproteins in pancreatic tissue and serum from mice with PDAC, pancreatic intra-epithelial neoplasia (PanIN) and matched healthy controls, using the well validated KPCB model of PDAC. Methods: Tryptic digests of protein extracts from snap frozen PDAC, pre-malignant and normal pancreata were subjected to solid-phase extraction of N-glycopeptides and the samples were analysed on a LTQ Orbitrap XL mass spectrometer. LC-MS feature maps were compared employing SuperHirn software and used for the label-free quantification of corresponding proteins. Primary mPDAC cell lines and their supernatants were also analysed. Selected candidate proteins were then quantified in mouse serum by SRM-based targeted proteomics. Results: 146 glycoproteins were identified as overexpressed by >2 fold (p<0.05, Student’s t test) in PDAC compared to normal pancreas and 60 were prioritised for targeted identification in mouse serum. 12 proteins were significantly upregulated (p<0.01, Mann-Whitney U test ) in the serum of tumour-bearing mice with PDAC compared to controls. Conclusions: Using a state of the art GEMM of PDAC, we have successfully applied a two-stage strategy for the tissue-based identification followed by quantification in murine serum of a panel of glycoproteins that are consistently over-expressed during mPDAC development. Validation in serum collections from patients with PDAC, chronic pancreatitis and healthy controls is underway and updated results will be presented at the conference.

Serum-Based Protein Biomarkers in Blast-Induced Traumatic Brain Injury Spectrum Disorder

The biological consequences of exposure to explosive blast are extremely complex. Serum protein biomarkers in blast-induced traumatic brain injury (bTBI) can aid in determining injury severity, monitoring progress, and predicting outcome. Exposure to blast results in varying degrees of physical injury. Explosive blast can also induce psychological stress that can contribute to or amplify the extent of physical damage. Given the complexity, scale of injury, and variety of symptoms, bTBI may be best described as a spectrum disorder. In this focused review, we summarize the status of serum protein biomarkers in bTBI in the context of the classification and pathological changes of other forms of TBI. Finally, we recommend specific and easily implementable measures to accelerate serum protein biomarker discovery and validation in bTBI.

Serum Proteomic Profiling Reveals That Pretreatment Complement Protein Levels are Predictive of Esophageal Cancer Patient Response to Neoadjuvant Chemoradiation

To identify serum-based biomarkers predicting response to neoadjuvant chemoradiotherapy (neo-CRT) in esophageal cancer. Increasingly, the standard of care for esophageal cancer involves neo-CRT followed by surgery. The identification of biomarkers predicting response to therapy may represent a major advance, enabling clinical trials and improved outcomes. Patients with esophageal cancer (n = 31) received a standard neo-CRT regimen. Histopathologic response to therapy was assessed by using the Mandard tumor regression grade (TRG) classification. Serum was collected pretreatment and at 24-hour and 48-hour time points into treatment. Serum samples were analyzed by using Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and enzyme-linked immunosorbent assay. A leave-one-out cross-validation predictive algorithm assessed the ability of validated biomarkers to correctly predict therapeutic outcome. Fifty-one percent (16) of patients were poor responders (TRG 3-5), whereas 49% (15) responded well (TRG 1-2). On CM10 biochips, serum expression of 9 protein peaks was significantly different between the response groups. Two differential spectrum peaks were identified as complement C4a and C3a and were subsequently analyzed by enzyme-linked immunosorbent assay. Pretreatment serum C4a and C3a levels were significantly higher in poor responders versus good responders. Subdivision of the response groups by TRG indicated an inverse correlation between levels of C4a and C3a and pathological response to neo-CRT. The leave-one-out cross-validation analysis revealed that these serum proteins could predict response to neo-CRT with a sensitivity and specificity of 78.6% and 83.3%, respectively. This translational application of proteomics technology identifies pretreatment serum levels of C4a and C3a as predictive biomarkers of response. Large validation studies in an independent cohort are merited.

Serumbiomarker für psychiatrische Erkrankungen

There are many challenges associated with the discovery and development of serum-based biomarkers for psychiatric disorders such as schizophrenia. Here, we review these challenges from the point of view of psychiatrists, the regulatory agencies and biomarker scientists. There is a general opinion in psychiatric medicine that improvements over the current subjective tests are essential. Despite this there is a reluctance to accept that peripheral molecules can do the job any better. In addition, psychiatrists find it difficult to accept that peripheral molecules, such as those found in blood, can reflect what is happening in the brain. However, the regulatory health authorities now consider biomarkers as important for the future of drug development and have called for efforts to modernize methods, tools and techniques for the purpose of developing more efficient and safer drugs. We also describe here the development of the first ever molecular blood-test for schizophrenia, and its reception in the market place, as a case in point.

Early Second-Trimester Serum MiRNA Profiling Predicts Gestational Diabetes Mellitus

BackgroundGestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM.Methodology/Principal FindingsWe systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16–19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222) were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1) expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2) in HepG2 cell lines.Conclusions/SignificanceSerum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.

Enzyme-based NAND gate for rapid electrochemical screening of traumatic brain injury in serum

We report on the development of a rapid enzyme logic gate-based electrochemical assay for the assessment of traumatic brain injury (TBI). The concept harnesses a biocatalytic cascade that emulates the functionality of a Boolean NAND gate in order to process relevant physiological parameters in the biochemical domain. The enzymatic backbone ensures that a high-fidelity diagnosis of traumatic brain injury can be tendered in a rapid fashion when the concentrations of key serum-based biomarkers reach pathological levels. The excitatory neurotransmitter glutamate and the enzyme lactate dehydrogenase were used here as clinically-relevant input TBI biomarkers, in connection to the low-potential detection of the NADH product in the presence of methylene green at a glassy carbon electrode. A systematic optimization of the gate and the entire protocol has resulted in the effective discrimination between the physiological and pathological logic levels. Owing to its robust design, the enzyme-based logic gate mitigates potential interferences from both physiological and electroactive sources and is able to perform direct measurements in human serum samples. Granted further detailed clinical validation, this proof-of-concept study demonstrates the potential of the electrochemical assay to aid in the rapid and decentralized diagnosis of TBI.

MiR-1254 and miR-574-5p: Serum-Based microRNA Biomarkers for Early-Stage Non-small Cell Lung Cancer

The ability to diagnose non-small cell lung cancer (NSCLC) at an early stage may lead to improved survival. The aim of this study was to identify differentially expressed serum-based microRNAs (miRNAs) between patients with early-stage NSCLC and controls. These miRNAs may serve as biomarkers for NSCLC early detection. miRNA profiling was performed on total RNA extracted from serum obtained from 22 individuals (11 controls and 11 patients with early-stage NSCLC). Quantitative polymerase chain reaction (qPCR) was used to validate the profiling results in the discovery set and in a validation set of 31 controls and 22 patients with early-stage NSCLC. Additionally, six matched plasma samples (four NSCLC cases and two controls) and three serum mesothelioma samples were analyzed by qPCR. Receiver operating characteristic curves were generated for each possible combination of the miRNAs measured by qPCR. The expression of hsa-miR-1254 and hsa-miR-574-5p was significantly increased in the early-stage NSCLC samples with respect to the controls. Receiver operating characteristic curves plotting these two miRNAs were able to discriminate early-stage NSCLC samples from controls with 82% and 77% of sensitivity and specificity, respectively, in the discovery cohort and with 73% and 71% of sensitivity and specificity, respectively, in the validation cohort. The mesothelioma and plasma samples did not seem to classify into either NSCLC or control groups. Serum miRNAs are differentially expressed between patients with early-stage NSCLC and controls. The utility of miR-1254 and miR-574-5p serum-based biomarkers as minimally invasive screening and triage tools for subsequent diagnostic evaluation warrants additional validation.

Challenges Related to Developing Serum-Based Biomarkers for Early Ovarian Cancer Detection

In this issue of the journal, Cramer and colleagues and Zhu and colleagues report carefully designed phase 3 assessments of candidate ovarian cancer screening biomarkers. The main conclusion is that CA-125 remains the "best of a bad lot"; the new candidates have fallen short of expectations. We review factors impeding the development of an effective ovarian cancer screening strategy, highlight the requirements related to validating proposed screening biomarkers, and emphasize the risks from premature clinical applications of unvalidated tests, all underscoring the need for new research strategies.

Sperm-Associated Antigen 9 Is a Novel Biomarker for Colorectal Cancer and Is Involved in Tumor Growth and Tumorigenicity

Colorectal cancer (CRC) is the second most common tumor in developed countries. The present study was undertaken to determine the expression of the sperm-associated antigen 9 gene (SPAG9) as a possible biomarker in CRC, to investigate its correlation with humoral immune response and different stages and grades in CRC patients, and to explore its possible role in colon tumorigenesis in vitro and in an in vivo mouse model. SPAG9 expression was determined by RT-PCR, in situ RNA hybridization, and immunohistochemistry. Humoral response against SPAG9 was detected by enzyme-linked immunosorbent assay and Western blotting. SPAG9 gene silencing was performed using plasmid-based small interfering RNA to study various malignant properties of colon cancer cells in vitro and in vivo. The majority of CRC patients showed SPAG9 expression and generated humoral response. There was a close relationship between SPAG9 protein expression and humoral immune response in the majority of early-stage CRC patients, indicating that anti-SPAG9 antibodies could be a novel serum biomarker for early diagnosis. The down-regulation of SPAG9 (mediated by small interfering RNA) inhibited malignant properties in in vitro and significantly suppressed tumor growth in vivo. These findings collectively suggest that SPAG9 may have a role in tumor development and early spread and thus could serve as a novel target for early detection and for cancer immunotherapy.

Biomarkers and Depressive Symptoms in a Sample of Cognitively Intact and Alzheimer’s Disease Elderly Males

Serum-based biomarkers and GDS-30 score and subscales of depressive symptoms were examined in a cross-sectional sample of 81 elderly men drawn from the TARCC cohort. Measurements included neuropsychological assessment and serum. Thirty three patients met consensus diagnosis for probable AD and forty eight were cognitively intact. Although initial regression analysis of all subjects showed significant relationships between depression and specific biomarkers, analyses based on diagnosis indicated that none of the biomarkers were significantly associated with depression among the controls. Among AD males MIF was significantly associated with total GDS scores and subscales of dysphoria, meaninglessness, and cognitive impairment. TNF-α was significantly associated with the apathy in AD males. Higher levels of MIF were associated with less depression in AD men. TNF-α was positively associated with degree of apathy. This study suggests the importance of cognitive status, gender and subtypes of depression when investigating biomarkers and depression in the elderly.

Abstract P1-07-01: Safety of High-Dose Vitamin D Supplementation in Premenopausal Women at High Risk for Breast Cancer

Abstract Background: Vitamin D has diverse biological effects on proliferation, differentiation, and apoptosis in multiple tissues, including the breast. Observational studies have demonstrated that serum 25-hydroxyvitamin D (25-OHD), an objective measure of vitamin D status, is inversely related to breast cancer risk, such that levels >40 ng/ml are associated with a 40% reduction in breast cancer risk compared to women who are vitamin D deficient (25-OHD <20 ng/ml). Serum 25-OHD above 32 ng/ml is thought to be sufficient for bone health and vitamin D toxicity occurs with levels above 150 ng/ml. However, uncertainty remains about whether vitamin D supplementation will reduce breast cancer risk, the optimal dose of vitamin D, and the target level of serum 25-OHD. We examined the safety of high dose vitamin D and the effects on serum 25-OHD in premenopausal women at high risk for breast cancer. Methods: Twenty high-risk premenopausal women (5-year Gail risk score ≥1.67%, history of LCIS or DCIS, BRCA1 or BRCA2 mutation carrier) were assigned to a 1-year intervention of cholecalciferol (vitamin D3) 30,000 IU weekly (cohort 1, N=10) or 20,000 IU weekly (cohort 2, N=8/10). Eligibility criteria included baseline serum 25-OHD ≥32 ng/ml and no history of kidney stones. Participants were monitored for toxicity, particularly hypercalcemia and hypercalciuria, every 3 months during the 1-year intervention. They underwent a digital mammogram and random core breast biopsy at baseline and 12 months, as well as serial blood collections at 0, 6, and 12 months. Serum 25-OHD was measured by Diasorin radioimmunoassay. Results: From November 2007 to March 2010, 18 of 20 participants were enrolled and 12 have completed the 1-year intervention (10 in cohort 1; 2 in cohort 2). Median age: 47 (37-52); White/Hispanic/Black: 8/9/1; Median body mass index: 27.7 kg/m2 (21.5-35.4); Elevated Gail risk/LCIS/DCIS: 11/6/1; Mean baseline serum 25-OHD: 19 ng/ml (11-27). Women assigned to a dose of 30,000 IU weekly (cohort 1) rose to a mean serum 25-OHD of 55 ng/ml (26-75) at 6 months and 59 ng/ml (49-71) at 12 months. The dose of 20,000IU weekly (cohort 2) resulted in a mean serum 25-OHD of 48 ng/ml (35-59) at 3 months and 50 ng/ml (42-63) at 6 months. No significant hypercalcemia (serum calcium >10.5 mg/dl) or hypercalciuria (spot urine calcium/creatinine >0.37) occurred at either dose level. One woman dropped out due to worsening gastroesophageal reflux symptoms. Biomarker analyses for samples collected from cohort 1 are ongoing. Discussion: We have demonstrated that a 1-year intervention of high-dose vitamin D3 20,000 IU or 30,000 IU weekly is well-tolerated and able to increase serum 25-OHD above 40 ng/ml in all participants, without any episodes of hypervitaminosis D. The effects of high-dose vitamin D on mammographic density, tissue and serum-based biomarkers of breast cancer risk are currently being evaluated. Large-scale randomized controlled trials are necessary to determine the safety, efficacy, optimal dose and duration of vitamin D supplementation for breast cancer chemoprevention. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-07-01.

Diagnostic relevance of circulating biomarkers in patients with lung cancer

Differential diagnosis of suspicious lung masses is essential for the selection of the appropriate therapy strategy. While non-small cell lung cancer (NSCLC) in early stages and single lung metastases from other cancers mostly are resected by surgery, late stage NSCLC, small cell lung cancers (SCLC) and multiple lung metastases are treated by systemic chemo- and/or radiotherapeutic approaches. In many patients, biopsies for the histopathological subtyping can not be taken due to multimorbidity and instable clinical conditions of the patient or unfavourable localisation of the tumor. In addition, heterogeneity of lung tumors may imply the presence of different malignant cell types in one suspicious lesion. As tumor-related biomarkers in blood reflect the biochemical properties of cancer cells, their release or non-release may be helpful to support the clinical decision making. This review summarizes the current knowledge about the potential and the role of serum-based biomarkers for the differential diagnosis of lung cancer which is also mirrored in the new recommendations of the National Academy of Clinical Biochemistry (NACB).

Identification of diagnostic serum protein profiles of glioblastoma patients

Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and is based on cerebral imaging and histological examination. Serum-based biomarkers may support detection of GBM. Here, we explored serum protein concentrations of GBM patients and used data mining to explore profiles of biomarkers and determine whether these are associated with the clinical status of the patients. Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differently expressed in tumors and in normal brain tissues. Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects. Data-mining methods involving all 14 proteins were used as an initial evaluation step to find clinically informative profiles. Data mining identified a serum protein profile formed by BMP2, HSP70, and CXCL10 that enabled correct assignment to the GBM group with specificity and sensitivity of 89 and 96%, respectively (p < 0.0001, Fischer’s exact test). Survival for more than 15 months after tumor resection was associated with a profile formed by TSP1, HSP70, and IGFBP3, enabling correct assignment in all cases (p < 0.0001, Fischer’s exact test). No correlation was found with tumor size or age of the patient. This study shows that robust serum profiles for GBM may be identified by data mining on the basis of a relatively small study cohort. Profiles of more than one biomarker enable more specific assignment to the GBM and survival group than those based on single proteins, confirming earlier attempts to correlate single markers with cancer. These conceptual findings will be a basis for validation in a larger sample size.

Exosomes: Extracellular organelles important in intercellular communication

In addition to intracellular organelles, eukaryotic cells also contain extracellular organelles that are released, or shed, into the microenvironment. These membranous extracellular organelles include exosomes, shedding microvesicles (SMVs) and apoptotic blebs (ABs), many of which exhibit pleiotropic biological functions. Because extracellular organelle terminology is often confounding, with many preparations reported in the literature being mixtures of extracellular vesicles, there is a growing need to clarify nomenclature and to improve purification strategies in order to discriminate the biochemical and functional activities of these moieties. Exosomes are formed by the inward budding of multivesicular bodies (MVBs) and are released from the cell into the microenvironment following the fusion of MVBs with the plasma membrane (PM). In this review we focus on various strategies for purifying exosomes and discuss their biophysical and biochemical properties. An update on proteomic analysis of exosomes from various cell types and body fluids is provided and host-cell specific proteomic signatures are also discussed. Because the ectodomain of ~42% of exosomal integral membrane proteins are also found in the secretome, these vesicles provide a potential source of serum-based membrane protein biomarkers that are reflective of the host cell. ExoCarta, an exosomal protein and RNA database (http://exocarta.ludwig.edu.au), is described.

Phase IB randomized, double-blinded, placebo-controlled, dose-escalation study of polyphenon E in women with a history of hormone receptor-negative breast cancer.

TPS142 Background: Priorities in breast cancer (BC) chemoprevention include developing agents effective against hormone receptor (HR)-negative BC and validating intermediate biomarkers which correlate with BC risk. Numerous epidemiologic and preclinical studies support the anti- cancer and chemopreventive effects of green tea in BC. The main polyphenol of green tea, epigallacatechin gallate (EGCG), is a potent antioxidant which acts on multiple stages of carcinogenesis. The central hypothesis of this proposal is that the green tea polyphenol mixture, polyphenon E (Poly E), has activity for the secondary prevention of HR-negative BC. The primary objective of this phase IB trial is to demonstrate the safety of using Poly E over a 6- month period in patients with a history of HR-negative BC. Secondary exploratory objectives are to investigate the dose-related biologic effects of Poly E on breast tissue, radiographic, and serum-based biomarkers. Methods: This trial is a phase IB, randomized, double-blind, placebo-controlled study of oral Poly E 400 mg, 600 mg, or 800 mg bid for 6 months in 40 women with a history of stage I-III HR-negative BC (minimum of 6 months since completing chemotherapy, radiation therapy, or surgery; age 21-65). To date 40 patients have been enrolled. The primary endpoint of this dose escalation study is to determine the maximum tolerated dose of Poly E in this patient population according to the time-to-event continual reassessment method. Safety is assessed by monitoring clinical and laboratory parameters monthly for the duration of the study. Patients undergo a random core biopsy and mammogram of the contralateral breast at baseline and 6 months and serial blood/urine collections every 2 months. Laboratory correlates include breast tissue-based biomarkers (Ki-67, cleaved caspase-3, ER, EGFR, p53), mammographic density, serum hormone metabolites (estradiol, testosterone, IGF-I, IGFBP-3, SHBG), inflammatory and oxidative stress biomarkers (serum CRP, urine PGE-M, 8-OHdG, isoprostane). This study tests the safety and potential efficacy of a novel BC chemopreventive agent and evaluates a new approach for testing these agents. No significant financial relationships to disclose.

Clinical biomarkers in esophageal adenocarcinoma

This review describes genetic and molecular changes related to adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) with emphasis on prognostic value and possibilities for targeted therapy in clinical setting. The progression of Barrett's esophagus to adenocarcinoma has been the focus of particular scrutiny, and a number of potential tissue and serum-based disease biomarkers have emerged. Tissue biomarkers allowing risk stratification of Barrett's are reviewed as well as strategies currently being used to discover novel biomarkers that will facilitate the early detection of esophageal adenocarcinoma.

Impact of diet and exercise intervention on breast ductal fluid among overweight postmenopausal women

Obesity and adulthood weight gain, operating through production of estrone in adipose tissue, inflammation, and obesity-related growth factors, increase breast cancer risk after menopause. Many studies have determined the systemic effects of excess adipose tissue on plasma and serum-based biomarkers, but few studies have determined the localized impact on biomarkers contained in breast ductal fluid. We are currently conducting a pilot 12-week diet and exercise weight-loss intervention among overweight postmenopausal women to evaluate changes in ductal fluid as a result of the intervention. To date, five women completed the study. We successfully obtained breast ductal fluid both before and after the intervention from four of the five women. Fluid was transferred into tubes and frozen in a -80° freezer. We are currently conducting assay measurements of hormones and biomarkers contained in ductal fluid. We observed changes in body composition and exercise parameters as a function of the intervention. Specifically, a 12% decrease in BMI (body-mass index), a 14% decrease in body fat mass, a 28% increase in aerobic fitness and 28% increase in muscle-strength occurred compared to baseline intervention measurements, among the women who completed the study. Our plans are to enroll five additional women, finish analyzing the ductal fluid biomarkers, and apply for a larger grant to expand the study.

Levels of 25-hydroxy-vitamin D in pre-menopausal women at high risk for development of breast cancer.

Abstract Abstract #5079 Background: There is biologic and epidemiologic evidence to suggest an inverse relationship between vitamin D intake and the risk of developing breast cancer, particularly for adolescent and premenopausal women. A recent meta-analysis of nested case control studies in an average risk cohort has suggested that those with &amp;gt;50 ng/ml of the pro-hormone 25-hydroxy-vitamin D, 25(OH)D, a good measure of recent vitamin D intake from all sources, have 50% fewer breast cancers than women with 25(OH)D levels regarded as severely deficient (&amp;lt;12 ng/ml) and 20% fewer breast cancers than those with levels regarded as deficient (12-20 ng/ml) or insufficient (20-30 ng/ml) [Garland et al. J Steroid Biochem Mol Biol 2007;103:708].&amp;#x2028; Materials and Methods: To determine if vitamin D supplementation should be explored as a prevention strategy in young women, we assessed the distribution of 25(OH)D levels in 100 high risk pre-menopausal women being screened for possible participation in Phase II prevention trials of a COX-2 inhibitor. These women were between the ages of 20 and 52, had undergone a random periareolar fine needle aspiration (RPFNA) and had serum frozen at -80°C within 2 months of the RPFNA. Serum was batch assayed for 25(OH)D, using the Liaison kit by DiaSorin (chemiluminescent assay) in a CLIA approved lab.&amp;#x2028; Results: Of 100 high risk women, 15% exhibited 25(OH)D levels considered severely deficient, 34% deficient, and 27% insufficient, Only 24% women exhibited 25(OH)D levels above 30 ng/ml, considered to be sufficient for bone health while only 4% had levels suggested as optimal for breast health. We have previously reported that high risk women with cytologic evidence of atypia had a 5 fold increase in their 4 year risk of developing DCIS or invasive cancer compared to those who do not [Fabian et al. J Natl Cancer Inst 2000; 92:1217]. Ninety-nine percent of women in our cohort were considered to have cytologic evidence of hyperplasia without (70%) or with (29%) atypia and median 25(OH)D levels were not different between samples regarded as hyperplastic and those assessed as atypical.&amp;#x2028; Discussion: These results indicate that 75% of high risk pre-menopausal women likely to participate in tissue biomarker-based chemoprevention trials will exhibit 25(OH)D levels that are insufficient for bone health and only 4% will have levels suggested from case control studies as being optimal for breast health. In this retrospective study, no association was observed between serum 25(OH)D levels (a marker of recent vitamin D intake) and a cytologic marker of increased breast cancer risk. A prospective trial is in progress to confirm the high prevalence of vitamin D insufficiency in young high risk women and to correlate 25(OH)D levels with a variety of tissue, imaging and serum-based risk biomarkers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5079.

IGF-I, IGFBP-3, and IGF-I/IGFBP-3 Ratio: No Association with Incident Colorectal Cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

The insulin-like growth factor (IGF) signaling system is thought to affect tissue growth and development ([1][1]), with IGF-I and IGF binding protein-3 (IGFBP-3) having putative procarcinogenic and anticarcinogenic properties, respectively. A recent meta-analysis of four prospective studies found

Plasma Protein Profiling by Mass Spectrometry for Cancer Diagnosis: Opportunities and Limitations

Plasma Protein Profiling by Mass Spectrometry for Cancer Diagnosis: Opportunities and Limitations