Biomarkers in cancer最新文献

OBJECTIVE: We evaluated the individual and combination effects of NAT1, NAT2 and tobacco smoking in a case-control study of 219 incident prostate cancer (PCa) cases and 555 disease-free men. METHODS: Allelic discriminations for 15 NAT1 and NAT2 loci were detected in germ-line DNA samples using TaqMan polymerase chain reaction (PCR) assays. Single gene, gene-gene and gene-smoking interactions were analyzed using logistic regression models and multi-factor dimensionality reduction (MDR) adjusted for age and subpopulation stratification. MDR involves a rigorous algorithm that has ample statistical power to assess and visualize gene-gene and gene-environment interactions using relatively small samples sizes (i.e., 200 cases and 200 controls). RESULTS: Despite the relatively high prevalence of NAT1*10/*10 (40.1%), NAT2 slow (30.6%), and NAT2 very slow acetylator genotypes (10.1%) among our study participants, these putative risk factors did not individually or jointly increase PCa risk among all subjects or a subset analysis restricted to tobacco smokers. CONCLUSION: Our data do not support the use of N-acetyltransferase genetic susceptibilities as PCa risk factors among men of African descent; however, subsequent studies in larger sample populations are needed to confirm this finding.

Background: Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis.

Objectives: To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers.

Methods: Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)-IgM directly in the peripheral blood sera of humans.

Results: Serum ANG-IgM levels are significantly higher in osteosarcoma patients than in healthy individuals (P < 0.005). Serum ANG-IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG-IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG-IgM levels were significantly higher in osteosarcoma patients compared to any other tumors (P < 0.001).

Conclusions: These results demonstrated that the combined biomarker ANG-IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG-IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.

Objective: The early detection of NSCLC is of importance because it provides chances for better outcomes. The aim of the study was to explore the clinical utility of EGFR and hTERT mRNA expression as markers for diagnosis of NSCLC.

Methods: EGFR and hTERT mRNA were quantified by quantative reverse transcription real time polymerase chain reaction in plasma of 45 non-small cell lung cancer (NSCLC) and 40 chronic obstructive pulmonary disease (COPD) patients, selected by certain spirometric characteristics that made them at high risk of developing lung cancer in future.

Results: The gene expression level of each gene was calculated and given as a relative quantity-RQ. EGFR gene expression was found in all lung cancer patients. The mean level of expression was RQ = 29.39. hTERT mRNA could be detected in 88% of patients. The mean expression ratio in them was RQ = 17.31. Only 50% of the high risk patients turned to be positive for EGFR. The level of their expression was RQ = 2.09. The plasma levels of hTERT could be detected in 17 (42.5%) patients of the high risk COPD group. Their mean level of expression was RQ = 1.02. A statistically significant difference in EGFR and hTERT mRNA expression could be observed between the two groups of patients-p = 0.0001.

Conclusion: EGFR and hTERT mRNA are potential markers for lung cancer diagnosis, whose clinical importance should be replicated in a larger cohort of patients.

Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies.

Glioma, the common brain tumor, which arises from the glial cells, offers worse prognosis and therapy than any other tumors. Despite the genetic and pathological diversities of malignant gliomas, common signaling pathways that drive cellular proliferation, survival, invasion and angiogenesis have been identified. Very often, various tyrosine kinase receptors are inappropriately activated in human brain tumors and contribute to tumor malignancy. During such tumourous states where multiple pathways are involved, a few of them are responsbile for cell differentiation, proliferation and anti-apoptosis. Computational simulation studies of normal EGFR signaling in glioma together with the mutant EGFR mediated signaling and the MAPK signaling in glioma were carried out. There were no significant cross talks observed between the mutant EGFR and the MAPK pathways and thus from the simulation results, we propose a novel concept of 'multiple-targeting' that combines EGFR and Ras targeted therapy thereby providing a better therapeutic value against glioma. Diallyl Disulfide (DADS) that has been commonly used for Ras inhibition in glioma was taken for analyses and the effect of inhibiting the EGFR downstream signaling protein with this DADS was analyzed using the simulation and docking studies.

Prostate cancer is the second most common cancer and the second leading cause of cancer death in men. However, prostate cancer can be effectively treated and cured, if it is diagnosed in its early stages when the tumor is still confined to the prostate. Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer. But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results. Epigenetic alterations including hypermethylation of gene promoters are believed to be the early events in neoplastic progression and thus these methylated genes can serve as biomarkers for the detection of cancer from clinical specimens. This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine.

A significant group of patient with estrogen receptor (ER) α positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERα status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERα (+) and ERα (-) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes (NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT-qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant over-expression of all the six genes in ERα (+) breast tumors as compared to ERα (-) breast tumors. In vitro studies using T-47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes (SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies "candidate biomarkers" that could be useful for predicting endocrine responsiveness.