PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy.

OBJECTIVE: The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1m) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB). METHODS: Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1m, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot. RESULTS: Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131-37.700), cytology (OR, 24.978; 95% CI, 3.085-540.236), and PAX1 methylation levels by grade (PAX1m grade) (OR, 7.801; 95% CI, 1.548-44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901-0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model's strong agreement between predicted and observed probabilities. CONCLUSION: The clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.

DNA repair in lung cancer: a large-scale quantitative analysis for polymorphisms in DNA repairing pathway genes and lung cancer susceptibility.

BACKGROUND: The results of associations between single nucleotide polymorphisms (SNPs) of genes in DNA repairing pathway and lung cancer (LC) risk are inconsistent. METHODS: We applied allele, dominant and recessive models to explore the risk of researched variants to LC in total LC and subgroups by ethnicity or LC subtypes with a cutoff point of p < 0.05. RESULTS: A total of 76,935 cases and 88,649 controls from 192 articles were included. Among the analyzed 40 variants from 20 genes, we found 9 statistically significant variants in overall populations by allele model, including five SNPs (rs1760944, rs9344, rs13181, rs1001581, and rs915927) increasing LC risk (odd ratios [ORs] = 1.10-1.71) and four SNPs (rs1042522, rs3213245, rs11615, and rs238406) decreasing the risk (ORs = 0.75-0.94). We identified rs1042522 and rs13181 as significant variants for LC in three models. Additionally, we identified differential significant SNPs in ethnic and subtype's analysis with comparison to total population. CONCLUSIONS: There are five SNPs in DNA repairing pathway associated with increased LC risk and four others decreased LC risk. Besides, the risky SNPs in different ethnicities and various LC subtypes were partly different, and the contribution of different genotypes to risk alleles were various as well.

High diagnostic value of miRNAs for NSCLC: quantitative analysis for both single and combined miRNAs in lung cancer.

BACKGROUND: MicroRNAs (miRNAs) are good candidates as biomarkers for Lung cancer (LC). The aim of this article is to figure out the diagnostic value of both single and combined miRNAs in LC. METHODS: Normative meta-analysis was conducted based on PRISMA. We assessed the diagnostic value by calculating the combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and the area under the curve (AUC) of single and combined miRNAs for LC and specific subgroups. RESULTS: A total of 80 qualified studies with a total of 8971 patients and 10758 controls were included. In non-small cell lung carcinoma (NSCLC), we involved 20 single-miRNAs and found their Sen, Spe and AUC ranged from 0.52-0.81, 0.66-0.88, and 0.68-0.90, respectively, specially, miR-19 with the maximum Sen, miR-20 and miR-10 with the highest Spe as well as miR-17 with the maximum AUC. Additionally, we detected miR-21 with the maximum Sen of 0.74 [95%CI: 0.62-0.83], miR-146 with the maximum Spe and AUC of 0.93 [95%CI: 0.79-0.98] and 0.89 [95%CI: 0.86-0.92] for early-stage NSCLC. We also identified the diagnostic power of available panel (miR-210, miR-31 and miR-21) for NSCLC with satisfying Sen, Spe and AUC of 0.82 [95%CI: 0.78-0.84], 0.87 [95%CI: 0.84-0.89] and 0.91 [95%CI: 0.88-0.93], and furtherly constructed 2 models for better diagnosis. CONCLUSIONS: We identified several single miRNAs and combined groups with high diagnostic power for NSCLC through pooled quantitative analysis, which shows that specific miRNAs are good biomarker candidates for NSCLC and further researches needed.

Chemotherapeutics for Acute Erythroid Leukemia: Research, Present and Future.

Acute erythroid leukemia (AEL) is a subtype of acute myeloid leukemia (AML) with features such as accumulation of maturation-arrested erythroblasts. Compared with AML, the progression of AEL is faster and the prognosis to available therapy is worse. However, its categorization is still being updated and the pathophysiology of AEL is still under research, making diagnosis and chemotherapy challenging for physicians. To achieve better outcomes, therapies should be optimized and new drugs should be developed. In this review, we summarize current strategies of diagnosis and therapies of AEL, and discuss prospective targets for chemotherapeutic agents based on the biological characteristics of AEL neoplastic cells as well as transcriptional factors and pathways related to erythroid differentiation.