Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.

Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection.

BACKGROUND: Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. METHODS: The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. RESULTS: We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. CONCLUSIONS: We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.

The possible association between the presence of an MPO -463 G > A (rs2333227) polymorphism and cervical cancer risk.

PURPOSE: The association between myeloperoxidase (MPO) polymorphism and the risk of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a correlation exists between MPO polymorphism and the risk for developing cervical cancer. METHODS: All case-control research studies that determined a relationship between MPO and cervical cancer reported up until March 1, 2018 in PubMed, Web of Science, VIP, WanFang, and the CNKI Database were accessed and included. The strength of association was evaluated with pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). We used sensitivity analysis to detect the stability of our results, conducted Q-test to evaluate heterogeneity and applied Begg's funnel plot and Egger's test to investigate any publication bias among selected studies. RESULTS: In this meta-analysis, we included 5 eligible studies in the final evaluation, which included 1125 patients with cervical cancer and 1150 cancer-free control patients. A potential association between the MPO -463 G > A polymorphism and cervical cancer risk was observed (recessive model: OR = 0.65, 95%, CI: 0.43-0.98, P = 0.038; homozygous model: OR = 0.65, 95%, CI: 0.43-0.99, P = 0.045), which indicates that genotype AA reduces the risk of cervical cancer by 35% compared to GG/GA or GG genotypes in our results. A stratified analysis by ethnicity identified a significant correlation among Caucasian patients (recessive model: OR = 0.57, 95%, CI: 0.34-0.95, P = 0.029; homozygous model: OR = 0.60, 95%, CI: 0.36-0.99, P = 0.048) and a stratified analysis by source of control identified a significant correlation among population-based studies. CONCLUSIONS: Our results suggest that the presence of polymorphism, -463 G > A in patients might offer them protection against cervical cancer. By implementing randomized case-control or cohort studies with larger sample sizes, the clinical significance of our results can be further strengthened and verified.