Diagnostic Marker For Early Diagnosis Research Articles

Risk Loci For Chronic Obstructive Disease Reside On Chromosome 14: A Case-Control Study On The Pakistani Population.

Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide, is characterized by airflow limitation that can be due to abnormalities in the airway and/or alveoli. Genetic diagnosis at an early stage can be a key factor in the provision of accurate and timely treatment. Single Nucleotide polymorphisms (SNPs) are an important tool to study genetic association/ predisposition of the disease and have great potential to be diagnostic markers for early diagnosis of disease. This case-control COPD association study was designed for the five SNPs residing on potential candidate genes (SERPINA1, SERPINA3, RIN3), to check whether these genes are involved in the genetic predisposition for COPD in the Pakistani population or not. The SNAPshot method was used to find out the risk alleles and haplotypes using ABI Genetic analyzer 3130. GeneMapper, Haploview and PLINK 1.9 software were used for analyzing the genotypes and haplotypes taking smoking exposure and gender as covariates. Two of the SNPs, rs4934 and rs17473 were found to be independently and significantly associated with COPD in our studied population whereas haplotype H1 for two SNPs, rs754388 and rs17473 (that are in high linkage disequilibrium), was found to be a significant risk factor for developing COPD symptoms. SNP variants of SERPINA1 and SERPINA3 are significantly and independently associated with COPD in the local population of Pakistan.

ATF3 as a potential diagnostic marker of early-stage osteoarthritis and its correlation with immune infiltration through bioinformatics analysis.

AimsThis study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue.MethodsThe gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed.ResultsA total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018).ConclusionATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression.Cite this article: Bone Joint Res 2022;11(9):679–689.

Potential biomarkers identified in plasma of patients with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Looking for reliable diagnostic markers for early diagnosis can reduce the impact of the disease on the fetus OBJECTIVE: The present study is designed to find plasma metabolites that can be used as potential biomarkers for GDM, and to clarify GDM-related mechanisms METHODS: By non-target metabolomics analysis, compared with their respective controls, the plasma metabolites of GDM pregnant women at 12-16 weeks and 24-28 weeks of pregnancy were analyzed. Multiple reaction monitoring (MRM) analysis was performed to verify the potential marker RESULTS: One hundred and seventy-two (172) and 478 metabolites were identified as differential metabolites in the plasma of GDM pregnant women at 12-16 weeks and 24-28 weeks of pregnancy, respectively. Among these, 40 metabolites were overlapped. Most of them are associated with the mechanism of diabetes, and related to short-term and long-term complications in the perinatal period. Among them, 7 and 10 differential metabolites may serve as potential biomarkers at the 12-16 weeks and 24-28 weeks of pregnancy, respectively. By MRM analysis, compared with controls, increased levels of 17(S)-HDoHE and sebacic acid may serve as early prediction biomarkers of GDM. At 24-28 weeks of pregnancy, elevated levels of 17(S)-HDoHE and L-Serine may be used as auxiliary diagnostic markers for GDM CONCLUSION: Abnormal amino acid metabolism and lipid metabolism in patients with GDM may be related to GDM pathogenesis. Several differential metabolites identified in this study may serve as potential biomarkers for GDM prediction and diagnosis.

Frequent expression of a novel cancer testis antigen, protein kinase human monopolar spindle 1 (hMps1/TTK) in human urinary bladder transitional cell carcinoma.

Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. The present study was undertaken to evaluate the mRNA and immunohistochemical (IHC) expression of protein kinase human monopolar spindle 1 (hMps1/TTK) gene in transitional cell carcinoma (TCC) of the bladder and correlate its expression with the clinicopathological characteristics of patients. In the present study, quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate TTK mRNA expression in TCC. IHC analysis of TTK was also evaluated. Independent Student's t, ANOVA and chi-square (χ2) tests were used to analyze the data statistically. The frequency of TTK mRNA over expression was detected in 50% of UBC (38/76) by qRT-PCR. Relative mean fold expression of TTK mRNA was found significantly (p < 0.05) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients (8.96 ± 4.51 vs. 5.64 ± 3.53, p = 0.03). Moreover, IHC reveals heterogenous immunostaining pattern of TTK in TCC tissues. The frequency of TTK protein over expression was detected in 56.9% (37 of 65) UBC patients. No significant IHC expression of TTK was detected among adjacent noncancerous tissues (ANCTs) and benign prostatic hyperplasia (BPH) used as control. Collectively our study observations conclude that TTK is a novel cancer/testis antigen (CTA) as a diagnostic marker for early diagnosis of UBC.

Diagnostic Significance of Serum Fatty Acid Synthase in Patients with Pancreatic Cancer.

BACKGROUND Pancreatic cancer is considered as the most deadly tumor among gastrointestinal cancers because of its poor prognosis. The frequently deregulated pathway in the cancer cell is associated with an increased expression of various genes, including the synthesis of fatty acids. We aimed to evaluate the level of serum fatty acid synthase (FASN) as a diagnostic marker for early diagnosis of pancreatic cancer. METHODS Serum FASN levels were measured by ELISA in 92 patients with pancreatic adenocarcinomas and in 92 healthy controls. Logistic regression analysis was used to identify independent predictors of certain diagnostic categories. RESULTS Serum FASN levels were significantly higher in patients with pancreatic cancer than in healthy controls (1.35 [0.98-2.3] ng/mL vs 1.04 [0.19-1.34] ng/mL, p < 0.001) and in smokers compared to non-smokers (1.41 [0.79-2.52] ng/mL vs 1.07 [0.21-1.74] ng/mL, p < 0.001). FASN levels and smoking were associated with increased risk of PC (1.54 [1.1- 2.14] ng/mL, p = 0.011 and 5.69 [2.68-12.09] ng/mL, p < 0.001, respectively). CONCLUSION Elevated serum FASN levels in patients with pancreatic cancer indicate the need for the production of large numbers of lipids for the survival and proliferation of human cancer cells and the diagnostic value of FASN as a new diagnostic biomarker.

MiRNA-208a in Acute Myocardial Infarction: Much more than a Cardiac Biomarker

Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Infarct size is the single most important predictor of adverse ventricular remodeling, and it is linearly dependent upon the amount of myocardial salvage by reperfusion. Lack of timely reperfusion, due to ineffective treatment or delayed presentation, leads to an unfavorable prognosis. Micro Ribo Nucleic Acids (miRNAs) are small non-coding RNAs ~22 nucleotides in length that function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathological processes in animals. The biogenesis of miRNAs is under tight control, and their dysregulation is associated with many human diseases. In cardiac diseases, including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered which leads to deleterious effects associated with heart injury, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them a promising diagnostic marker for early diagnosis of acute MI. The great cardio-specific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. in this review we will illustrate the role of miRNA-208a in human heart and its therapeutic implications.

MicroRNA-125b-5p is a promising novel plasma biomarker for alveolar echinococcosis in patients from the southern province of Qinghai

BackgroundAlveolar echinococcosis (AE) is caused by parasitic infection by Echinococcus multilocularis. Its diagnosis is usually based on clinical symptoms, ultrasound, and other imaging methods. MicroRNAs (miRNAs) play important roles in disease processes and can exist in a highly stable cell-free form in body fluids. It is important to identify specific, sensitive diagnostic markers for early diagnosis and evaluation of AE. In this study, we examined hsa-miR-125b-5p as a potential plasma biomarker of E. multilocularis infection.MethodsPlasma samples from patients with AE and healthy individuals were screened for the presence of five miRNAs using miRNA chips. We used quantitative polymerase chain reaction to measure miRNA expression levels in plasma and liver tissue samples from patients with AE.Resultshsa-miR-125b-5p was stably upregulated in the plasma and liver tissue samples from patients with AE.ConclusionsThe results suggest that hsa-miR-125b-5p may be a promising biomarker for early, non-invasive diagnosis of AE.

Evaluation of hematological parameters in oral cancer and oral pre-cancer

Background: Oral squamous cell carcinoma (OSCC) is the most common public health issue in Indian population. Quite a large number of OSCC cases are preceded by potentially malignant disorders of oral cavity. The need for simple diagnostic marker for early diagnosis and thus better therapeutic outcome is imperative. The current study aims to evaluate hematological parameters such as hemoglobin, bleeding time, clotting time, total leucocyte count (TLC) and differential leucocyte count (DLC) in OSCC and oral potentially malignant disorder cases along with normal healthy controls.Methods: A total of 150 subjects; 50 in each group were taken and 2.5 ml of blood were withdrawn from each subject and TLC, DLC and hemoglobin assessment was done using autoanalyzer while bleeding time and clotting time was recorded through Duke’s method and modified Dale’s method respectively.Results: All the data were tabulated and recorded as mean±standard deviation and comparison was done using one-way ANOVA test (p&lt;0.05). TLC count, neutrophil count and lymphocyte count showed statistically significant difference amongst three groups while other parameters such as hemoglobin percentage, bleeding time, clotting time, eosinophil count, monocyte count and basophil count were statistically non-significant.Conclusions: This study showed TLC count, neutrophil count and lymphocyte count might prove as useful determinant factor in oral squamous cell carcinoma and oral potentially malignant disorders. However, further study with larger sample size is required to establish their role as diagnostic, prognostic marker or predictor of malignant transformation.

Abstract A13: DNA methylation of SOX1 and HOXA9 as a biomarker for early detection of ovarian cancer in cell-free DNA

Abstract Background: Accumulated evidence revealed that aberrant CpG island hypermethylation plays significant roles in carcinogenesis that can serve as a promising target for molecular detection in body fluids. Ovarian cancer remains the most lethal gynecologic malignancy and is characterized by few early symptoms, late stage presentation, and resulting poor survival, which thereby renders challenge to its prompt diagnosis. Despite a myriad of attempts at early diagnosis of ovarian cancer, this clinical aim still remains a major challenge. To date, no single biomarker is able to accurately detect early OC in either tissue or body fluid. Aberrant circulating DNA methylation patterns provide highly specific cancer signals. Methods: To develop a DNA methylation-based screening assay for early diagnosis of ovarian cancer, we quantitatively assessed the promoter methylation of DAPK1, HOXA9, RASSF1A, and SOX1 genes in 105 ovarian cancer and 30 non-neoplastic ovarian specimens by means of a high-throughput quantitative, real-time PCR-based technique (MethyLight) and clonal bisulfite sequencing. The best-performing gene cassette was further evaluated for their methylation status in cell-free DNA from serum of matched 35 ovarian cancer patients and 20 normal controls. Area under the ROC (Receiver-operator characteristic) curve was used to evaluate the discriminatory performance of both individual and combined gene panel. Results: RASSF1A, HOXA9, DAPK1, and SOX1 displayed a methylation frequency of 72.72, 82.67, 68.0, and 80.0%, respectively, in tissue samples. We identified DNA methylation of HOXA9 and SOX1 as the best discriminator between cancer and non-neoplastic tissue. In the multiplex assay, the combined panel of HOXA9 and SOX1 achieved a sensitivity of 88.0% with a specificity of 86.7%, when either or both of the gene promoters showed methylation. These genes appear to have great potential to be evaluated for their methylation level in cell-free DNA as a noninvasive diagnostic marker for early diagnosis of ovarian cancer. In cell-free DNA, this novel panel achieved a sensitivity of 62.86.0% and a specificity of 95% with an area under the ROC curve of 0.81 for discriminating OC samples from normal control. The results of MethyLight were concordant with those of clonal bisulfite sequencing. Conclusion: Our findings revealed the potential of epigenetic biomarker for early detection of OC in cell-free DNA as a minimally invasive tool. Here, we have established that promoter hypermethylation can be detected in serum cell-free DNA from patients with early as well as advanced-stage ovarian cancer. Based on the multiplex MethyLight assay, study will focus on analyzing the clinical utility of HOXA9 and SOX1 as methylation biomarkers. These findings further underline the potential of multiplexing individual markers into a panel that helps to achieve higher sensitivity and specificity than individual marker and provides robustness to a noninvasive early screening test. Citation Format: Alka Singh, Jaydeep Aravindbhai Badarukhiya, Sameer Gupta, Manisha Sachan. DNA methylation of SOX1 and HOXA9 as a biomarker for early detection of ovarian cancer in cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A13.

Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women.

PurposeLiterature emerging from Western countries has reported increased levels of serum oxidative stress markers among polycystic ovarian syndrome (PCOS) women. In the Arab region, there is limited research about the association between oxidative stress and PCOS. This study aimed to compare sociodemographic and clinical characteristics, sex hormones, and oxidative stress indices between PCOS women and non-PCOS women and to investigate the correlation between oxidative stress biomarkers and sex hormones.MethodsThis hospital-based case-control study was conducted among reproductive-aged women. The study included 51 women diagnosed with PCOS (as per Rotterdam 2003 criteria) and 45 control women who were not diagnosed with PCOS. Serum samples were collected to measure the mean levels of the following sex hormones: total testosterone, dehydroepiandrosterone sulfate, estradiol and progesterone, as well as to measure biomarkers of oxidative stress including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione (GSH), and total antioxidant capacity (TAC).ResultsPCOS women exhibited clinical characteristics including irregular menses, hirsutism, and acne compared to the control group (P≤0.05). Significant differences were observed in the waist-hip ratio of PCOS women compared to controls (P=0.004). GPx and GR activity levels appeared to be higher among PCOS women compared to controls; however, no statistically significant differences were observed between the two groups (P>0.05). PCOS women had lower GSH and TAC levels compared to controls with a statistically significant difference observed for GSH levels (P=0.006). Correlation analysis showed a significant negative correlation between estradiol and TAC in the total sample (r=−0.284, P=0.005).ConclusionThis study provides supportive evidence that oxidative stress might play a role in the pathogenesis of PCOS and, hence, oxidative stress parameters could be suggested as diagnostic markers for early diagnosis of high-risk groups. Also, the study provides supportive evidence that obesity and sex hormones, particularly estradiol, in PCOS may contribute to enhanced oxidative stress.

Association of Oxidative Stress with Polycystic Ovarian Syndrome in Oman: A Case‐Control Study

BackgroundPrevious studies in Euro‐American populations have shown that women with polycystic ovarian syndrome (PCOS) have increased levels of serum oxidative stress markers. In the Arab region, there is noticeable lack of research of the association between oxidative stress and PCOS.ObjectiveThis study aims to compare socio‐demographic, clinical characteristics and oxidative stress indices between women diagnosed with PCOS and non‐PCOS women.MethodsThis hospital based case‐control study was conducted among women aged 16–49 years. The study included 51 women diagnosed with PCOS (as per Rotterdam 2003 criteria) and 45 control women who were known not to have PCOS. Serum blood samples were collected to measure biomarkers of oxidative stress including glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and total antioxidant capacity (TAC) using commercially available kits.ResultsReduced GSH levels (P= 0.006) were significantly lower among PCOS women compared to non PCOS women. GR and GPx activity levels showed higher trends in women with PCOS compared to non PCOS women and the difference was significant for the GPx activity (P= 0.04). PCOS women also showed lower TAC levels (P= 0.08) than the control group with no significant difference between the two groups.ConclusionThe study provides a supportive evidence for the association between oxidative stress and PCOS among Omani women. Oxidative stress might play a role in pathogenesis of PCOS, so these parameters may be suggested as diagnostic markers for early diagnosis and screening of high risk groups.Support or Funding InformationSultan Qaboos UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis.

Breast cancer (BC) is the most common female malignancy within the spectrum of human cancer. One promising way to reduce the mortality and morbidity of BC is to explore novel diagnostic markers for early diagnosis and prognostication. The neutrophil lymphocyte ratio (NLR) is a good reflection of inflammation, which plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear. The aim of this meta-analysis is to explore the prognostic value of NLR in BC. Among the screened references in the database, 12 eligible studies were identified in this study. Patients with a higher NLR had a shorter disease-free survival (hazard ratio =1.46, 95% confidence interval: 1.12–1.90, P=0.044) and overall survival (hazard ratio =2.03, 95% confidence interval: 1.41–2.93, P<0.001). In the subgroup analysis of NLR and disease-free survival, the studies from Eastern countries had a positive result with perfect homogeneity (I2=0); however, this homogeneity has not been achieved in studies from Western countries. In the subgroup analysis of the NLR and overall survival, the results of the univariate and multivariate analyses were completely different, with different heterogeneity. In the luminal A and luminal B subtypes, we found that there was no association between the NLR and overall survival in the BC patients. Positive results were obtained in the analyses of the human epidermal growth factor receptor 2 (HER2)-positive and triple-negative BC subtypes. In conclusion, this meta-analysis suggests that NLR is a good prognostic marker for BC, and patients with a higher NLR have poorer prognoses. Future studies should perform more detailed investigations to decrease heterogeneity and determine the appropriate cut-off values for different races.

The Diagnostic Value of Neutrophil CD64 in Detection of Sepsis in Children

Background: Pediatric sepsis is a life-threating condition that requires instant management. The choice of the best biomarker and its best cut-off value is critical for diagnosis of infection in children especially with the delay in obtaining the culture results. Objective: The main objective of this study was to evaluate the diagnostic value of neutrophil CD64 in early diagnosis of sepsis among children. Methodology: This prospective study was conducted on 50 children with suspected sepsis and 50 control children without infection. Blood samples were taken on admission for blood culture. Detection of neutrophil CD64 (nCD64) was carried out by flow cytometry and CRP was measured by ELISA. Results: CD64 was elevated significantly in sepsis compared to the control group. There was a significant difference between the levels of nCD64 in culture positive cases (80%) compared to culture negative ones (20%). Neutrophil CD64% was highly predictive of childhood sepsis with are under the curve (AUC) =1. Conclusion: Neutrophil CD64% is a very good diagnostic marker for early diagnosis of sepsis with a higher sensitivity than CRP.

Identification of a three-miRNA signature as a blood-borne diagnostic marker for early diagnosis of lung adenocarcinoma.

BackgroundThe subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed.ResultsBased on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA–based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer.MethodsTwo hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system.ConclusionsTaken together, these findings suggest that the 3 miRNA–based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma.

Procalcitonin and C-reactive protein in early diagnosis of neonatal sepsis

ABSTRACT Background Blood culture is the gold standard for diagnosis of neonatal sepsis, however culture negative sepsis is suspected by high C-reactive protein (CRP) and procalcitonin (PCT) levels. The aim of this study was to compare the diagnostic accuracy of PCT as compared to CRP in diagnosis of neonatal sepsis. Methods Blood samples of 200 neonates with 98 sepsis group and 102 non-sepsis group were analysed for CRP, PCT and culture from December 2012 to July 2013. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of PCT was determined compared to CRP. Results The study group included 56% male and 44% female babies. CRP was raised in 65/98 whereas PCT in 76/98 in sepsis group and in non sepsis group it was 24/102 for CRP and 21/ 102 for PCT. Sensitivity, specificity, positive predictive value, and negative predictive value of PCT was 77.55%, 79.41%, 78.35% and 78.64% respectively as compared to 66.33%, 76.47%,73.03%, 70.27% for CRP respectively. Diagnostic accuracy of PCT was higher at 78.5% as compared to 71.5% for CRP. Conclusion PCT is a better diagnostic marker for early diagnosis of neonatal sepsis as compared to CRP, where blood culture though a gold standard for diagnosis of neonatal sepsis, shows growth in only around 23% of sepsis cases. Diagnosis of neonatal sepsis by blood culture takes up to 72 h and hence use of PCT as a diagnostic marker can minimise this delay in diagnosis. Copyright © 2014, Indian Journal of Medical Specialities. Published by Reed Elsevier India Pvt. Ltd. All rights reserved.

Neutrophil CD64 as a Diagnostic Marker of Sepsis in Neonates

BackgroundSepsis in neonates hospitalized in the neonatal intensive care unit is a global problem and is a significant contributor to morbidity and mortality. Neutrophil surface CD64, the high-affinity Fc receptor,...

Abstract 4934: Employing the Berg Interrogative Biology® systems platform to elucidate cellular signaling changes that contribute to the pathophysiology of hepatocellular carcinoma (HCC)

Abstract Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, ranked as the third most fatal cancer after lung and stomach carcinomas. The diverse etiology, high morbidity/mortality, lack of diagnostic markers for early diagnosis and the highly variable clinical course of HCC have hindered advances in diagnosis and treatment. After years of studying the HCC, the understanding of molecular mechanism operational in HCC remains incomplete. The genomic, transcriptomic and comparative proteomic profiles have yielded some important insights for HCC research. However, many studies focused on single aspect of the cellular changes associated with HCC, hindering the full understanding of biological systems in their true complexity and dynamics. We describe a novel approach combining the power of cell biology, integrated proteomics platforms and an informatics platform that generates causal protein networks. In order to delineate the role of post-translation modification and enzymes that partake in such mechanisms, we incorporated activity based proteomics employing kinase enrichment probes and phosphoproteome mapping of total proteins in HCC cellular models. Multikinase inhibitor Sorafenib, the first line chemotherapeuitc agent for the advanced HCC patients, was used to probe the global kinase activity and protein phosphorylation changes associated with this treatment. Comparative proteomics, phosphoproteome and kinase activity data was integrated into the AI based REFS™ informatics platform. Causal networks of protein interaction specifically from a functional stand point namely kinase activity and potential targets that kinases can phosphorylate were generated. In addition, using cellular functional read out, proteins/ kinases that modulate phosphorylation of targets and mechanistically drive pathophysiological cellular behavior were determined. The approach outlined here enables global characterization of cellular responses, insights into mechanisms of chemo sensitivity and potential targets/biomarkers for clinical management of HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4934. doi:1538-7445.AM2012-4934

Abstract 3023: MicroRNA expression profile in pancreatic cancer stem cells

Abstract MicroRNA(or miRNA) regulates various biological process including development, differentiation, proliferation, maintenance and apoptosis. Recently, existence of cancer stem cells was reported in some solid malignancies, including breast, brain, prostate, liver and pancreas cancers. Pancreatic ductal adenocarcinoma remains an extremely aggressive malignancy that is virtually therapy-resistant. Thus better understanding on cancer stem cell biology will not only help us to develop diagnostic marker for early diagnosis but also to treat against chemoresistant pancreatic cancer. Lately, evidences of miRNA involvement in cancer stem cells have been reported. Several miRNAs including let-7, mir-200, and mir-181 shows regulatory functions in cancer stem cells of different organs, however, miRNAs in other cancers including pancreas has not yet been reported. In this present study, we analyzed pancreatic cancer stem cell specific miRNAs and further investigated their functional role in cancer stem cells. To analyze the differentially expressed miRNAs, we used sphere cultivation methods to enrich stem cell population and analyzed overall miRNA expression with miRNA microarray. Then correlation of miRNA expression and mRNA expression was analyzed by using linear model Yijkg=µ+Ai+Dj+Vk+Gg+AGig+VGkg+εijkg where A, D, V, and G represent the additive effect of the ith array, jth dye, kth biological group, and gth gene, respectively; AG represents the combinatorial effect of the ith array with the gth gene; εijkg describes the random error associated with each measurement; and VG for the combinatorial effect of the kth biological group with the gth gene. All additive effects were estimated via least squares and an F-test was performed on the modeled data to select differentially expressed genes. The candidate miRNA expression was confirmed by qRT-PCR. As a result, number of miRNAs showed differential expression in sphere and are considered to have functional role in cancer stem cells by directly or indirectly targeting mRNAs. Further, correlation analysis suggested possible linkage between miRNA clusters with stem cell associated mRNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3023.

Serum myeloperoxidase: a novel biomarker for evaluation of patients with acute coronary syndrome

ObjectivesMyeloperoxidase, an abundant leucocyte enzyme, is elevated in culprit lesions that have ruptured in patients with sudden cardiac injury. Multiple lines of evidence suggest an association between myeloperoxidase and inflammation...

High-dimensional biology to comprehend hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is the third leading cause of death from cancer. The diverse etiology, high morbidity/mortality, lack of diagnostic markers for early diagnosis and the highly variable clinical course of HCC have hindered advances in diagnosis and treatment. Microsatellite instability, chromosomal aberrations, mutations in key cell cycle genes and epigenetic changes have been reported in HCC. Availability of modern technologies advance ‘high-dimensional biology’ (HDB), a term that refers to the simultaneous study of the genetic variants (genome), transcription (mRNA; transcriptome), peptides and proteins (proteomics), and metabolites (metabolomics) for the intermediate products of metabolism of an organ, tissue or organism. The growing interest in omics-based research has enabled the simultaneous examination of thousands of genes, transcripts and proteins of interest, with high-throughput techniques and advanced analytical tools for data analysis. The use of each approach towards functional omics has lead to the classification of HCC into molecular subgroups. Here we review the use of HDB as a tool for the identification of markers for screening, diagnosis, molecular classification and the discovery of new therapeutic drug targets of HCC. With the extensive use of HDB, it may be possible in the near future, to have custom-made therapeutic regimens for HCC based on the molecular subtype, ultimately leading to an improved survival of HCC patients.