[Show abstract][Hide abstract] ABSTRACT: Ovarian cancer is one of the leading causes of cancer-related deaths among women. There is an urgent need of better approaches for the identification of appropriate biomarkers in the early detection of ovarian cancer. The aim of this study was to elucidate the significance of autoantibodies against insulin-like growth factor II mRNA-binding proteins (IMPs) in patients with ovarian cancer. In this study, autoantibody responses to two members (IMP1 and p62/IMP2) of IMPs were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting, and indirect immunofluorescence assay in sera from patients with ovarian cancer and normal human individuals. The results have demonstrated that both IMP1 and p62/IMP2 can induce relatively higher frequency of autoantibody responses in patients with ovarian cancer (26.5% and 29.4%) compared to normal individuals (P < 0.01). Our preliminary data suggest that IMP1 and p62/IMP2 can stimulate autoimmune responses in ovarian cancer, and anti-IMP1 and anti-p62/IMP2 autoantibodies could be used as potential biomarkers in immunodiagnosis of ovarian cancer.
Research Journal of Immunology 01/2014; 2014:326593.
[Show abstract][Hide abstract] ABSTRACT: To determine whether a panel of multiple tumor-associated antigens (TAAs) would enhance antibody detection, the diagnostic value of autoantibodies to a panel of multiple TAAs in cancer has been evaluated. The TAAs used in this study was composed of eight TAAs including Imp1, p62, Koc, p53, C-myc, Cyclin B1, Survivin, and p16 full-length recombinant proteins. Enzyme-linked immunosorbent assay and immunoblotting were used to detect antibodies in 304 cancer sera and also 58 sera from normal individuals. The antibody frequency to any individual TAA in cancer was variable but rarely exceeded 20%. With the successive addition of TAAs to a final combination of total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 63.5% and a specificity of 86.2% in the combined cancer group. In different types of cancer, the ranges of positive and negative likelihood ratio were 4.07-4.76 and 0.39-0.51, respectively, and the ranges of positive and negative predictive values were 74.2-88.7% and 58.8-75.8%, respectively. Agreement rate and Kappa value were 67.1% and 0.51, respectively. These results further support our previous hypothesis that detection of anti-TAAs autoantibodies for diagnosis of certain type of cancer can be enhanced by using a miniarray of several TAAs.
Journal of immunology research. 01/2014; 2014:512540.
[Show abstract][Hide abstract] ABSTRACT: Peroxiredoxin 1 (Prdx1) is an antioxidant and plays an important role in H2O2-mediated cell signaling. We previously found that the expression level of Prdx1 was elevated in esophagus squamous cell carcinoma (ESCC) tissue using a proteomics approach. Since overexpressed protein can induce an autoimmune response, to further examine whether serum from ESCC patients exhibits immunoreactivity against Prdx1, autoantibody responses to Prdx1 were evaluated by ELISA, western blotting and indirect immunofluorescence assay in sera from patients with ESCC and normal individuals. Immunohistochemical study with tissue array slides and western blot analysis with cancer cell lines were also performed to analyze the protein expression profiles of Prdx1 in ESCC tissues and cancer cell lines. The results demonstrated that the positive rate of autoantibody against Prdx1 in ESCC sera was 13.2% (9/68), whereas this rate was 0% (0/89) in normal individuals. Data also showed that expression of Prdx1 was significantly increased in ESCC tissues when compared to expression in paired adjacent normal tissues (P<0.05). The data indicate that Prdx1 may contribute to malignant transformation of the esophagus, and may be used as a biomarker in the immunodiagnosis of ESCC.
[Show abstract][Hide abstract] ABSTRACT: Since intracellular proteins involved in carcinogenesis have been shown to provoke autoantibody responses, autoantibodies can be used as probes in immunoproteomics to isolate, identify, and characterize potential tumor-associated antigens (TAAs). Once a TAA is identified, several approaches will be used to comprehensively characterize and validate the identified TAA/anti-TAA systems that are potential biomarkers in certain types of cancer. Our ultimate goal is to establish rigorous criteria for designation of an autoantibody to a TAA as a cancer biomarker, examine candidate TAAs for sensitivity and specificity of anti-TAA antibody response, and further develop customized TAA arrays that can be used to enhance anti-TAA antibody detection in cancer. This review will mainly focus on the recent advances in our studies using immunoproteomic approach to identify and characterize TAAs as biomarkers in cancer.
[Show abstract][Hide abstract] ABSTRACT: Sera from patients with cancer contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). This study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in breast cancer detection and diagnosis. The mini-array of multiple TAAs was composed of ten TAAs, including Imp1, p62, Koc, p53, c-myc, survivin, p16, cyclin B1, cyclin D1 and CDK2 full-length recombinant proteins. An enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against these ten TAAs in 41 sera from patients with breast cancer, as well as 82 sera from normal individuals. The antibody frequency of the individual TAAs in breast cancer was variable and ranged between 7.3 and 22.0%. With the successive addition of TAAs to a final total of ten antigens, there was a stepwise increase in positive antibody reactions, reaching a sensitivity of 61.0% and a specificity of 86.6% in breast cancer. The positive and negative likelihood ratios were 5.545 and 0.438, respectively, which showed that the clinical diagnostic value of a parallel assay of eight TAAs was high. The positive and negative predictive values were 73.5 and 82.0%, respectively, indicating that the parallel assay of eight TAAs raised the diagnostic precision significantly. The agreement rate and κ-value were 79.7% and 0.52, respectively, while the Youden's Index (YI) was 0.5, indicating that the observed value of this assay had a middle range coincidence with the actual value. The data from the present study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of certain types of cancer may be enhanced using a mini-array of several TAAs as target antigens. A customized antigen mini-array using a panel of appropriately selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of breast cancer.
[Show abstract][Hide abstract] ABSTRACT: CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-myc in human malignancies. Autoantibodies to CIP2A protein have been reported to be present in higher levels in sera from patients with hepatocellular carcinoma (HCC) than in sera of healthy individuals. The CIP2A gene has been demonstrated as a potential cancer susceptibility gene. To elucidate whether common CIP2A variants are associated with HCC susceptibility, we conducted a case-control study comprising 233 cases of HCC and 280 controls matched on age, gender and ethnicity in the Chinese Han population. Two haplotype-tagging single nucleotide polymorphisms (htSNPs) (rs2278911 and rs4855656) from the HapMap database were analyzed, which provide an almost complete coverage of the genetic variations in the CIP2A gene. We found that neither of these htSNPs and haplotypes were associated with the risk of HCC. However, an interaction was observed between hepatitis virus B and C infection (HBV and HCV) and the C carriers (TC or CC) of rs2278911 on HCC risk (OR=12.35; 95% CI, 4.93-19.87). No such association was found for rs4855656. Our study also demonstrated that two htSNPs (rs2278911 and rs4855656) in the CIP2A gene are not associated with the risk of HCC. HBV and HCV infection was found to exert a synergistic effect on the risk of HCC in individuals with the C carriers (TC or CC) of rs2278911 in the Chinese Han population.
[Show abstract][Hide abstract] ABSTRACT: A number of studies have shown that cyclooxygenase-2 (COX-2) gene polymorphisms were associated with gastric cancer. However, the results from different research groups have not been consistent. The present study aimed to investigate the association between polymorphisms of the cyclooxygenase-2 promoter region (-1195G>A, -765G>C) and gastric cancer patients with various degrees of relationship in the Chinese Han population. COX-2-1195G>A and COX-2-765G>C polymorphisms in 296 gastric cancer patients and 319 control family members were genotyped using polymerase chain reaction-restriction fragment length polymorphism. An increased risk of gastric cancer was observed in subjects with the COX-2-1195AA genotype (OR=2.03; 95% CI, 1.27-3.22), and the association strength decreased as the degree of relationship decreased. Stratification analysis revealed that the OR value of COX-2-1195AA genotype and A carriers exhibited synergy with Helicobacter pylori (H. pylori) infection (AA genotype: OR=2.96; 95% CI, 1.57-5.58; A carriers: OR=2.04; 95% CI, 1.18-3.52). No significant difference was found in each genotype of COX-2-765G>C between gastric cancer patients and control family members, as well as gastric cancer patients with various degrees of relationship. Our study demonstrated that the polymorphism of COX-2-1195AA genotype may be a risk factor for gastric cancer patients with various degrees of relationship among the Chinese Han population. H. pylori infection therefore may enhance the risk of gastric cancer in individuals with the COX-2-1195 AA genotype.