EPB41L3 (Erythrocyte Membrane Protein Band 4.1 Like 3)

In contrast, the performance was suboptimal in women aged <30 years (sensitivity, 33.33%; AUC, 0.64). The host multigene DNA methylation assay demonstrates high specificity and good sensitivity for triaging HPV-positive ASC-US women, with the potential to reduce colposcopy referrals while maintaining robust detection of high-grade lesions, particularly in those aged ≥30 years.

Compared to cytology triage testing, DNA methylation triage analysis using our three-marker panel offers an appropriate alternative to detect CIN3+ in hrHPV-positive vaginal self-samples. Implementation of the DNA methylation triage test would not only increase cancer detection, but would also eliminate the need for physician visits for cytological triage testing. In addition, it would accelerate referral decisions, ultimately reducing uncertainty and ensuring timely screening completion for all women.

EPB41L3 expression is lower and the methylation level is higher in glioma, which not only play roles in tumour suppression but also are related to prognosis and the tumour immune microenvironment. EPB41L3 can be used as a prognostic and therapeutic biomarker for glioma.

Our approach outperforms two other leading methods, yielding robust findings and identifying novel differentially methylated cytosines. We found that CRC patient survival time follows a two-component mixture regression model, where genes CDH11, EPB41L3, and DOCK2 are active in the more aggressive form of CRC, whereas TMEM215, PPP1R14A, GPR158, and NAPSB are active in the less aggressive form.

The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937-0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening.

In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications.

Our report provides the first clinical description of an autosomal recessive disorder associated with variants in EPB41L3, which we refer to as EPB41L3-associated developmental disorder (EADD). Moreover, our functional studies substantiate the pathogenicity of EPB41L3 hypothesized loss-of-function variants.

Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

EPB41L3 suppresses the progression of CC via activating the ERK/p38 MAPK pathway. EPB41L3 may serve as an effective therapeutic target for CC.

This new panel, consisting of ITGA4, ASCL1, and FAM19A4, has a sensitivity of 84% and a specificity of 70%, similar to our previously identified panel (ANKRD18CP, LHX8, and EPB41L3). Thus, in addition to our previously identified panel, the combination of ITGA4, ASCL1, and FAM19A4 showed good diagnostic performance and potentially can replace cytology, thereby avoiding additional doctor's visits for many women worldwide and reducing the time for decision-making for referral to the gynecologist.

We found that our study through this integrative approach an efficient tool and paved a new way to prioritize the candidate genes and these genes could be evaluated experimentally for potential validation. We suggest this may be useful in analyzing the nucleotide sequences and protein sequences for clustering, classification, class affiliation, etc.

HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management.