Jianying Zhang

Association of interleukin-1 gene polymorphisms with gastric cancer: A meta-analysis

Previous studies on the association between interleukin‐1 (IL‐1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL‐1 genotype and gastric caner by systematically reviewing the risk of the original studies. Thirty‐nine studies, which included 6,863 gastric cancer cases and 8,434 controls, met the inclusion criteria and were included in the meta‐analysis. By pooling all the studies identified, the summary odds ratio (OR) of gastric cancer risk associated with IL‐1B–511T, −31C, +3954T and IL‐1RN*2 was 1.26 (95% confidence interval (CI): 1.03–1.55), 1.00 (95% CI: 0.82–1.22), 1.37 (95% CI: 0.94–2.00) and 1.20 (95% CI: 1.01–1.41), respectively. A stratified analysis showed that IL‐1B–511T was associated with an increased risk of gastric cancer (intestinal type) (OR = 1.76, 95% CI: 1.12–2.57). Moreover, IL‐1RN*2 was also associated with an increased risk of gastric cancer among Caucasians (OR = 1.30, 95% CI: 1.09–1.54). In conclusion, IL‐1B–511 and IL‐1RN genetic polymorphisms are associated with an increased risk of developing gastric cancer.

XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case–control studies

X-ray repair cross-complementing group 1 gene (XRCC1) has been implicated in risk for lung cancer. However, the results from different studies remain controversial. In this meta-analysis, we have assessed 44 published case–control studies regarding associations of lung cancer risk with three common polymorphisms, codon 194, codon 280 and codon 399, and −77 Txa0>xa0C in the promoter region of XRCC1. The results in total population showed that the risk for lung cancer was increased among the variant homozygote Trp/Trp of codon 194 polymorphism, compared with the wild type Arg/Arg (OR: 1.19; 95xa0% CI 1.01–1.39), and the variant genotype CC of −77 Txa0>xa0C polymorphism showed a significantly increased risk of developing lung cancer, compared to wild-type genotype TT (OR: 1.91; 95xa0% CI 1.24–2.94). However, no associations were found between lung cancer risk and codon 280, codon 399. In the subgroup analyses by ethnicity, the OR for the variant homozygote Trp/Trp of codon 194 was 1.21(95xa0% CI 1.02–1.43) for Asian. When stratified by source of control, we found a protective effect of codon 194 Arg/Trp genotype (OR: 0.87; 95xa0% CI 0.77–0.98) and risk effect of codon 399 combined Arg/Glnxa0+xa0Gln/Gln variant genotype (OR: 1.09; 95xa0% CI 1.01–1.18) for lung cancer on the basis of hospital control. Subgroup analyses by histological types of lung cancer indicated that the heterozygote Arg/Trp in codon 194 could decrease and the combined variant genotype Arg/Glnxa0+xa0Gln/Gln in codon 399 could increase the risk of non-small cell lung cancer (OR: 0.69; 95xa0% CI 0.57–0.85 and OR: 1.14; 95xa0% CI 1.04–1.24). In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and −77 Txa0>xa0C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer. To further evaluate effect of XRCC1 polymorphisms, gene–gene interaction and gene-environment interaction on lung cancer risk, a single large sample size study with thousands of subjects is required to get conclusive results.

Competing endogenous RNA networks and gastric cancer.

Recent studies have showed that RNAs regulate each other with microRNA (miRNA) response elements (MREs) and this mechanism is known as competing endogenous RNA (ceRNA) hypothesis. Long non-coding RNAs (lncRNAs) are supposed to play important roles in cancer. Compelling evidence suggests that lncRNAs can interact with miRNAs and regulate the expression of miRNAs as ceRNAs. Several lncRNAs such as H19, HOTAIR and MEG3 have been found to be associated with miRNAs in gastric cancer (GC), generating regulatory crosstalk across the transcriptome. These MRE sharing elements implicated in the ceRNA networks (ceRNETs) are able to regulate mRNA expression. The ceRNA regulatory networks including mRNAs, miRNAs, lncRNAs and circular RNAs may play critical roles in tumorigenesis, and the perturbations of ceRNETs may contribute to the pathogenesis of GC.

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.

Prediction of near-term risk of developing breast cancer using computerized features from bilateral mammograms

Asymmetry of bilateral mammographic tissue density and patterns is a potentially strong indicator of having or developing breast abnormalities or early cancers. The purpose of this study is to design and test the global asymmetry features from bilateral mammograms to predict the near-term risk of women developing detectable high risk breast lesions or cancer in the next sequential screening mammography examination. The image dataset includes mammograms acquired from 90 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including image preprocessing, suspicious region segmentation, image feature extraction, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under curve (AUC) is 0.754±0.024 when applying the new computerized aided diagnosis (CAD) scheme to our testing dataset. The positive predictive value and the negative predictive value were 0.58 and 0.80, respectively.

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

AIMnTo identify biomarkers for diagnosis and prognosis of hepatocellular carcinoma (HCC).nnnMETHODSnScreening the HCC cDNA library with HCC patients sera. Isolated proteins were used as antigens to detect antibodies from patients with HCC and control sera.nnnRESULTSnEighty-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.nnnCONCLUSIONSnHCC associate antigens identified from this study supply candidate markers of diagnosis, combined detection and immunotherapy of HCC.

Serum autoantibodies in the early detection of esophageal cancer: a systematic review

Antibodies against tumor-associated antigens (TAAs) have been found in serum of patients with various types of cancers and may serve as biomarkers for early detection of esophageal cancer as well. This systematic review aims to give an overview about known autoantibodies and their diagnostic value in esophageal cancer. We conducted a systematic literature search in two databases to identify studies which performed serological testing for autoantibodies in esophageal cancer patients and controls. Data on study characteristics and results were extracted independently by two reviewers. Overall, 45 articles reporting the detection of 35 different autoantibodies met the inclusion criteria of this review. The most common antibody detection method was enzyme-linked immunosorbent assay (ELISA), and the most frequently assessed autoantibody was anti-p53, which was tested in 17 studies and for 15 studies of which a meta-analysis was conducted to comprehensively evaluate the diagnostic value. Most antibodies were assessed in only one study, and only few authors have evaluated the diagnostic value of combinations of multiple autoantibodies. For single autoantibodies, specificity was generally very high (median 98.3xa0%), but sensitivity was mostly rather low (median 26.7xa0%). For some autoantibody combinations, substantially higher sensitivity at reasonably high levels of specificity could be achieved. Development of extended and optimized multimarker panels of autoantibodies might be a promising approach for esophageal cancer early detection.

Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: Based on published genome-wide association studies in a central Chinese population

A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G>T and rs2274224 C>G) of PLCE1 in a population-based case-control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45-5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46-0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (Ptrend=0.005). The Grs17417407Ars2274223Crs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62-0.93), meanwhile the Grs17417407Grs2274223Crs2274224 and Trs17417407Grs2274223Crs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33-2.18 and OR, 2.51; 95% CI, 1.15-2.49). Gene-environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the high risk group with 3.67-fold (OR: 3.67, 95% CI: 2.74-4.92), compared to the low risk group. Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.