To evaluate the diagnostic values of using autoantibodies in sera to a panel of eight tumor-associated antigens (TAAs) of P53, Koc, P62, C-myc, IMP1, Survivn, P16 and Cyclin B1 full-length recombinant proteins for early detection of patients with gastric cardia adenocarcinoma (GCA) and high-risk subjects screening. Enzyme-linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 383 sera samples from four groups, including 140 subjects with normal gastric cardia epithelia (NOR), 76 patients with chronic atrophic gastritis (CAG), 79 patients with gastric cardia dysplasia (DYS) and 88 patients with GCA. In addition, the expression of the eight antigens was analyzed in gastric cardia tissues by immunohistochemical method. The individual autoantibodies to six TAAs (P53, P62, IMP1, Survivn P16 and Cyclin B1) were significantly higher in sera from patients with GCA than that in normal subjects (P < 0.05). When autoantibody assay successively accumulated to seven TAAs (P53, Koc, P62, C-myc, IMP1, Survivn and P16), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (13% in NOR, 39% in CAG, 46% in DYS, and 64% in GCA, respectively), the risks to CAG, DYS and GCA steadily increased about 4.4-, 5.7- and 12.0-fold. The sensitivity and the specificity for autoantibodies against the seven TAAs in diagnosing GCA reached up to 64% and 87%, respectively. The area under the receiver operating characteristic curve for the seven anti-TAA autoantibodies was 0.73 (95%CI: 0.68-0.78) No more increase in sensitivity was found with the addition of new anti-TAA autoantibodies. A combination detection of autoantibodies to TAAs might be helpful to distinguish GCA patients from normal subjects and the patients with gastric cardia precancerous lesions. In addition, further studies in patients with GCA and precancerous lesions using enlarged TAA panels might improve the sensitivity and specificity of cancer detection and high-risk subjects screening.
Background and purpose: Soluble ST2 (sST2) is a promising biomarker in inflammation, atherosclerosis and cardiovascular diseases. We investigated the association between serum sST2 and poor outcome in patients with transient ischaemic attack (TIA)/ischaemic stroke. Methods: Patients within 24 h after onset and with measured serum sST2 were prospectively enrolled in this study. Poor outcome was a combination of a new stroke event (ischaemic or haemorrhagic) and all-cause death within 90 days and 1 year. The associations of serum sST2 with poor outcome were analysed by Cox proportional hazards. Results: Among the 430 patients included, the median (interquartile range) sST2 was 17.72 (9.31-28.84) ng/mL. A total of 19 (4.4%) and 38 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Compared with the lowest sST2 tertile, hazard ratios (HRs) [95% confidence intervals (CI)] for the highest tertile were 5.14 (1.43-18.51) for poor outcome within 90 days and 3.00 (1.29-6.97) at 1 year after multivariate adjustments. Adding sST2 to a prediction model significantly improved risk stratification of poor outcome in TIA/ischaemic stroke, as observed by the continuous net reclassification improvement of 60.98% (95% CI, 15.37-106.6%, P = 0.009) and integrated discrimination improvement of 2.63% (95% CI, 0.08-5.18%, P = 0.043) at 90 days and the continuous net reclassification improvement of 41.68% (95% CI, 8.74-74.61%, P = 0.013) at 1 year. Conclusions: Increased serum sST2 levels in TIA/ischaemic stroke were associated with increased risks of poor outcome within 90 days and 1 year, suggesting that serum sST2 may be a potential long-term prognostic biomarker for TIA/ischaemic stroke.
Background:We previously reported frequent loss of heterozygosity on the short arm of chromosome 1 (1p) in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) as well as chronic myeloid leukemia (CML) to blast crisis. Methylation in a promoter CpG of several tumor suppressor genes has been associated with loss or decreased expression in tumors. We previously reported methylation of the PRDM2 gene in MDS. We also found that the PRDM2, RUNX3, and TP73 genes on 1p36 were frequently methylated in CML. Aims: To elucidate the relevance of tumor suppressor genes on 1p, we extended analysis of promoter methylation and expression of the PRDM2, RUNX3, and TP73 genes in MDS and AML. Methods: Mononuclear cells were isolated from bone marrow or peripheral blood samples after obtaining written informed consent from 34 patients with MDS, 17 patients with secondary AML from MDS, and 55 patients with de novo AML. The 34 MDS samples consisted of 13 RA, 1 RARS, 10 RAEB, 6 RAEB-t, 4 CMML and the 55 AML consisted of 1 M0, 12 M1, 17 M2, 7 M3, 8 M4, 7 M5, 1 M6, and 2 M7 (FAB classification). This study was performed according to ethical criteria of our institute. Genomic DNA was treated with bisulfite, and treated DNA was subject to amplification with HotStarTaq Master Mix Kit for MS-PCR. Bisulfite sequence was performed in both directions. Quantitative real time reverse transcriptase-PCR was performed in 26 patients of which RNA was suitable for analysis. HL-60 myeloid leukemia cells were grown in RPMI 1640 in the presence of 5-Aza-dC. The correlation between the frequency of methylation and type of disease or clinical characteristics was analyzed using the chi-square test or Fisher's exact probability test. Analysis was performed using SPSS Software. Results: PRDM2 methylation was detected in 17/34 MDS (50%) and 22/72 AML patients (31%) (p = 0.053). It was detected in 11/17 secondary AML (65%), and 11/55 de novo AML patients (20%) (p = 0.0005). Methylation of the RUNX3 gene was detected in 0/14 MDS, 0/7 secondary AML, and 2/30 de novo AML patients (7%). Methylation of the TP73 gene was observed in 1/14 MDS (7%), 0/7 secondary AML, and 4/32 de novo AML patients (13%). Bisulfite sequence revealed methylation at many CpG sites in the promoter of the PRDM2 gene. PRDM2 expression (mean) was not significantly different in secondary AML and de novo AML (2.026 vs. 1.900, p = 0.815). PRDM2 expression (mean) was not significantly different in methylation-positive group and methylation-negative group (1.996 vs. 1.810, p = 0.728). In comparison with expression of normal bone marrow cells, decreased PRDM2 expression was accompanied by methylation in 6/9 patients examined. Decreased PRDM2 expression was also observed in 7/13 patients without methylation. Decreased RUNX3 expression was observed in 5/5 MDS, 5/5 secondary AML, and 12/14 de novo AML patients. Decreased TP73 expression was observed in 2/4 MDS, 2/4 secondary AML, and 6/13 de novo AML patients. 5-Aza-dC treatment of HL-60 cells (that have methylation in PRDM...
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