1.
Screening and clinical evaluation of dominant peptides of centromere protein F antigen for early diagnosis of hepatocellular carcinoma.
Li, S, Li, X, Xu, A, Zhang, B, He, X, Chen, H, Huang, J
Molecular medicine reports. 2018;(3):4720-4728
Abstract
Tumor-associated antigens, such as centromere protein F (CENP‑F), have been recognized as potential serological biomarkers for early diagnosis of hepatocellular carcinoma (HCC); however, the exact regions corresponding to the dominant peptides of CENP‑F antigen remain to be explored. We aimed to screen and evaluate potential dominant peptides of CENP‑F for early diagnosis of HCC. Dominant peptides of CENP‑F were predicted by BioSun version 3.0, and the corresponding recombinant proteins were prepared. Enzyme‑linked immunosorbent assays were conducted for initial screening of dominant peptides, and selected dominant peptides were subjected to further clinical evaluation. Eight dominant peptides of CENP‑F antigens were predicted at amino acids (a.a) 121‑220, 335‑416, 1100‑1265, 1670‑1791, 1759‑2093, 2075‑2210, 2485‑2592, and 2808‑2960. Initial screening of the predicted peptides in samples of 47 HCC cases showed the highest diagnostic value for 121‑220 a.a and 1670‑1791 a.a peptides with area under the curve (AUC) values of 0.795 [95% confidence interval (CI), 0.706‑0.884] and 0.809 (95% CI, 0.721‑0.896), sensitivity of 58.3 and 85.4%, and specificity of 93.9 and 65.3%, respectively. Further evaluation of the two peptides in 405 samples comprised of 153 HCC, 126 liver cirrhosis and 126 healthy controls, presenting an AUC of 0.743 (95% CI, 0.674‑0.812) for 121‑220 a.a peptide in detecting early‑stage HCCs. Specifically, the 121‑220 a.a peptide showed a complementary effect in combination with α‑fetoprotein (AFP) for the detection of early‑stage HCC with increased AUC value of 0.840 (95% CI, 0.781‑0.899), and sensitivity of 81.4% and specificity of 72.2%. In conclusion, our study identified the 121‑220 a.a dominant peptide as the region of CENP‑F antigen with the highest immunogenicity and demonstrated its value in combination with AFP for diagnosis of early-stage HCC.
2.
Association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma risk: a systematic review and meta-analysis.
Peng, Q, Li, S, Lao, X, Chen, Z, Li, R, Qin, X
Medicine. 2014;(29):e330
-
-
Free full text
-
Abstract
Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065-1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099-1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141-1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy-Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.