Kaijuan Wang

Evaluation of Tumour-Associated Antigen (TAA) Miniarray in Immunodiagnosis of Colon Cancer

Previous studies demonstrated that cancer sera contain antibodies, which react with a unique group of autologous cellular antigens called tumour‐associated antigens (TAAs). This study determines whether a mini‐array of multiple TAAs would enhance antibody detection and be a useful approach in colon cancer detection and diagnosis. The mini‐array of multiple TAAs was composed of five TAAs including Imp1, p62, Koc, p53 and c‐myc full‐length recombinant proteins. Enzyme‐linked immunosorbent assay (ELISA) was used to detect antibodies against these five TAAs in 46 sera from patients with colon cancer and also 58 sera from normal individuals. Antibody frequency to any individual TAA in colon cancer was variable and ranged from 15.2% to 23.9%. With the successive addition of TAAs to a final total of five antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 60.9% and a specificity of 89.7% in colon cancer. Positive and negative likelihood ratio was 5.91 and 0.43 respectively, which showed that the clinical diagnostic value of parallel assay of five TAAs was high. Positive and negative predictive values were respectively 82.4% and 74.3% indicating that parallel assay of five TAAs raised the diagnostic precision greatly. Agreement rate and Kappa value were 76.9% and 0.52 respectively, which indicated that the observed value of this assay had middle range coincidence with actual value. The data from this study further support our previous hypothesis that detection of autoantibodies for diagnosis of certain type of cancer can be enhanced by using a mini‐array of several TAAs as target antigens. In 19 colon cancer sera with carcinoembryonic antigen (CEA) negative, 11 (57.9%) were found to have anti‐TAA antibodies. When CEA and anti‐TAAs were used together as markers in colon cancer detection, the diagnostic sensitivity could be raised from 60.9% to 82.6%. A customized antigen mini‐array using a panel of appropriately selected TAAs can enhance autoantibody detection in immunodiagnosis of colon cancer. Anti‐TAA and CEA were independent markers and the simultaneous use of these two markers significantly raised the sensitivity of colon cancer detection.

Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of breast cancer

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.

XRCC1 gene polymorphisms and esophageal squamous cell carcinoma risk in Chinese population: A meta-analysis of case―control studies

Two non‐synonymous polymorphisms Arg194Trp and Arg399Gln in the DNA‐base excision repair gene X‐ray repair cross‐complementing group 1 (XRCC1) have been implicated in risk for esophageal cancer. However, the results from different studies remain controversial. The present meta‐analysis of literatures was performed to clarify these associations in Chinese population. A comprehensive literature search was conducted to identify all case–control studies of XRCC1 polymorphisms Arg194Trp and Arg399Gln and risk for esophageal squamous cell carcinoma (ESCC). A total of 9 eligible studies, including 1,538 ESCC cases and 2,472 controls, were identified to the meta‐analysis. The odds ratio (OR) for the variant homozygous genotype Trp/Trp of the Arg194Trp polymorphism, compared with the wild‐type homozygote Arg/Arg, was 1.59 (p = 0.0007), with 95% confidence interval (95% CI) 1.22–2.09, for ESCC risk without between‐study heterogeneity. However, there was no statistically significant associations of ESCC risk in the dominant model Arg/Trp+Trp/Trp (OR 0.97; 95% CI 0.84–1.12; p = 0.69) and heterozygous genotype Arg/Trp (OR 0.90; 95% CI 0.77–1.04; p = 0.16) when comparing with wild‐type genotype Arg/Arg. For Arg399Gln, there was no effect in dominant modeling (Arg/Gln+Gln/Gln vs. Arg/Arg: OR 0.92; 95% CI 0.80–1.06; p = 0.25), and the variant Gln/Gln homozygote was not associated with ESCC risk (OR 1.29; 95% CI 0.79–2.10; p = 0.31), either. In conclusion, Arg194Trp genetic polymorphism may be associated with an increased risk for developing ESCC and a study with the larger sample size is needed to further evaluate gene–environment interaction on XRCC1 polymorphisms and ESCC risk.

Identification of tumor-associated antigens by using SEREX in hepatocellular carcinoma

AIM To identify biomarkers for diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS Screening the HCC cDNA library with HCC patients sera. Isolated proteins were used as antigens to detect antibodies from patients with HCC and control sera. RESULTS Eighty-one positive clones were identified. The frequencies of autoantibody against five HCC-associated antigens were higher in HCC than that in chronic hepatitis and normal human sera. The sensitivity and specificity of KRT23, AHSG and FTL antigens combination tests up to 98.2% in joint test and 90.0% in series test separately. CONCLUSIONS HCC associate antigens identified from this study supply candidate markers of diagnosis, combined detection and immunotherapy of HCC.

Polymorphisms in lncRNA HOTAIR and susceptibility to breast cancer in a Chinese population.

Controversial data have emerged on the association between cancer risk and the single-nucleotide polymorphism (SNP, rs920778C>T) in Hox transcript antisense RNA (HOTAIR). No data on the association between HOTAIR polymorphism and breast cancer (BC) susceptibility and reproductive factors have been reported in China. In this study we investigated the association between HOTAIR polymorphisms and BC susceptibility in a population-based case-control study of 502 cases and 504 matched controls in China. Three haplotype tagging SNPs (rs1899663, rs4759314, rs920778) of HOTAIR were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created-restriction-site PCR (CRS-RFLP) assays. False-positive report probability (FPRP) was calculated to test for false-positive associations. Interactions between the SNPs and reproductive factors were further evaluated by the multifactor dimensionality reduction (MDR) method. BC risk reduction was confined to subgroups of age at menarche >14 (OR: 0.42, 95%CI: 0.21, 0.82) and number of pregnancies >2 (OR: 0.65, 95%CI: 0.49, 0.95) for GT+TT rs1899663, and age at menopause ≤ 50 (OR: 0.97, 95%CI: 0.84, 0.99) for AG+GG rs4759314. Subjects with Trs920778 had a significantly increased risk of breast cancer (OR: 1.41, 95%CI: 1.13, 1.75). We observed a significant interaction between rs920778 and reproductive factors, including age at menopause, number of abortions, and family history. Our results were unlikely to be false positives according to FPRP calculation. In conclusion, genetic variant rs920778 in HOTAIR significantly increased the risk of BC, and it may have apparent interaction with reproductive factors in the progression on BC. These findings extend available data on the association between HOTAIR polymorphisms and BC susceptibility.

Genetic Polymorphisms in Long Noncoding RNA H19 Are Associated With Susceptibility to Breast Cancer in Chinese Population.

AbstractH19, a maternally expressed imprinted gene transcribing a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. However, the association between the H19 polymorphisms and breast cancer (BC) susceptibility has remained elusive. The aim of this study was to evaluate the associations between 2 H19 haplotype tagging SNPs (rs3741219 T>C, rs217727 C>T) and the risk of breast cancer.Our study comprised 464 BC patients and 467 cancer-free controls in China. rs3741219 and rs217727 were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created restriction site PCR (CRS-RFLP) assays, respectively. False-positive report probability (FPRP) was calculated to test the false-positive association.On performing univariate analysis, no significant association between H19 polymorphisms (rs3741219 and rs217727) and BC was observed. However, in further stratified analyses, CT+TT genotypes of rs217727 had a significantly lower risk of breast cancer among women with number of pregnancy >2 (OR = 0.79; 95% CI = 0.55–0.97). CT genotype of rs217727 was associated with ER positivity (OR = 2.19; 95 % CI = 1.07–4.45) and HER-2 positivity (OR = 1.34; 95 % CI = 1.05–2.12). It was proved that our results were less likely to be false positives according to false-positive report probability calculation.Our findings extend available data on the association of H19 polymorphisms and BC susceptibility. Further validation in large population or cohort studies is needed.

Comparison of visceral and body fat indices and anthropometric measures in relation to untreated hypertension by age and gender among Chinese

BACKGROUND The aim of the study was to compare the efficiency of bioelectrical indices (percentage body fat, PBF; visceral fat index, VFI) and various anthropometric measures (body mass index, BMI; waist circumference, WC; waist-to-height ratio, WHtR) on determining hypertension in Chinese. METHODS We conducted the community-based cross-sectional survey during August of 2013 to August of 2015 in 66 sample sites selected by multistage random sampling method from Henan province. 14,364 residents were included in the study. RESULTS In both genders, VFI and PBF tended to rise with age. However, for each age-specific group, men consistently had significantly greater VFI than women (all P<0.0001) and women had considerably higher PBF (all P<0.0001). The odds ratios and area under the ROC curves (AUCs) for hypertension associated with adiposity indices decreased with age. In younger (15~34year) men and women, VFI had the highest crude (2.43-7.95) and adjusted (2.40-11.63) odds ratio for hypertension. The AUCs for PBF, VFI and WHtR were significantly larger than those for BMI and WC (all P<0.01). Whereas no statistically significant difference were found in AUCs among PBF, VFI and WHtR (all P>0.10). Additionally, VFI and PBF yielded the greatest Youden index in identifying hypertension in men (0.27) and women (0.34), respectively. Optimal cutoffs for VFI/PBF were 11.70/24.45 and 7.55/33.65 in men and women, respectively. CONCLUSIONS VFI and PBF could be better candidates for identifying hypertension in men and women, respectively. Adolescents and young adults should be highlighted in preventing hypertension by control of excess body and visceral fat.

Tumour-Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta-Analysis.

Tumour‐associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour‐associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour‐associated autoantibody was included in a meta‐analysis, and its clinical value was determined using Fagans nomogram. The analysis included 84 studies regarding tumour‐associated autoantibodies with the diagnostic value. Anti‐p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour‐associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme‐linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti‐p53 antibody was included in a meta‐analysis. When it had been detected using ELISA and cut‐off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagans nomogram showed post‐test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour‐associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour‐associated autoantibodies as biomarkers for BC detection, a high‐quality prospective study is needed to validate their diagnostic value in practice.

Reduced red blood cell count predicts poor survival after surgery in patients with primary liver cancer

Abstract Currently, the optimal therapy of primary liver cancer (PLC) remains to be hepatic resection. For better management of the patients, we evaluated the prognostic predicting value of red blood cell (RBC) count, a routine laboratory parameter, on the long-term survival of patients who underwent surgical treatment. Clinical and laboratory data of 758 patients, who underwent surgical hepatic resection, were retrospectively studied by χ2 tests and logistic regression. All patients were enrolled at Henan Cancer Hospital, Zhengzhou, China, from February 2009 to July 2013, and none of them received any other treatments before surgery. Kaplan–Meier survival analysis and Cox proportional hazard models were used to examine the influence of RBC counts on patients’ survival. The Cox univariate and multivariate analyses showed that preoperative RBC count was an independent risk factor of poor prognosis after surgical treatment. The Kaplan–Meier curves showed that the overall survival (OS) of patients without reduced preoperative RBC counts was significantly better than those patients with reduced preoperative RBC counts (P < 0.001). Concordantly, compared with the patients with either reduced preoperative and/or postoperative RBC counts, patients without reduced RBC counts preferred to be low Child–Pugh grades (P = 0.0065), which implies a better hepatic function. In addition, low RBC count was found to be significantly associated with patients of female (P = 0.003), younger age (P =  < 0.001), and with higher AST/ALT ratio (P = 0.005). This study revealed that patients with preoperative RBC counts lower than normal had worse OS rates than those without reduced preoperative RBC counts, perhaps due to the significant correlation of reduced preoperative RBC count to patients’ worse Child–Pugh grade that reflect the loss of liver functions.

Genetic variants in lncRNA SRA and risk of breast cancer

Long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) has been identified to activate steroid receptor transcriptional activity and participate in tumor pathogenesis. This case-control study evaluated the association between two haplotype tagging SNPs (htSNPs) (rs10463297, rs801460) of the whole SRA sequence and breast cancer risk. We found that rs10463297 TC genotype significantly increased BC risk compared with CC genotype in both the codominant (TC vs. TT: OR=1.43, 95 % CI=1.02–2.00) and recessive (TC+CC vs. TT: OR=1.39, 95 % CI=1.01–1.92) genetic models. Both TC, TC + CC genotypes of rs10463297 and GA, AA, GA+AA genotypes of rs801460 were significantly associated with estrogen receptor (ER) positivity status. rs10463297 TC (2.09 ± 0.41), CC (2.42 ± 0.51) and TC + CC (2.20 ± 0.47) genotypes were associated with higher blood plasma SRA mRNA levels compared with the TT genotype(1.45 ± 0.34). Gene–reproductive interaction analysis presented a best model consisted of four factors (rs10463297, age, post-menopausal, No. of pregnancy), which could increase the BC risk with 1.58-fold (OR=1.58, 95 % CI=1.23–2.03). These findings suggest that SRA genetic variants may contribute to BC risk and have apparent interaction with reproductive factors in BC progression.