Muhammad Habiburrahman

Clinical validation of a DNA methylation biomarker associated with overall survival of relapsed ovarian cancer patients

Abstract Approximately 70% of ovarian cancer (OC) patients relapse after chemotherapy, underscoring the need to assess survival before second‐line treatment. We previously identified PLAT‐M8, an 8‐CpG blood‐based methylation signature linked to chemoresistance. This study validates its correlation with clinicopathological features and treatment profiles in additional cohorts. Extracted DNA from whole blood was provided from the BriTROC‐1 ( n  = 47) and OV04 cohorts ( n  = 57) upon the first relapse. Additional samples from Hammersmith Hospital ( n  = 100) were collected during first‐line chemotherapy (Cycles 3–4 and 6). Bisulphite pyrosequencing was used to quantify DNA methylation at the previously identified 8 CpG sites. The methylation data obtained were combined with previous data from ScoTROC‐1D and 1V ( n  = 141) and OCTIPS ( n  = 46). Cox regression was used to assess OS after relapse concerning clinicopathological characteristics. The DNA methylation Class (Class 1 vs. 2) was determined by consensus clustering. As for results, blood DNA methylation at relapse correlates with clinical outcomes, but it has no impact during first‐line treatment. Class 1 is linked to shorter survival (summary OS: HR 2.50, 1.64–3.79) and poorer prognosis on carboplatin monotherapy (OS: aHR 9.69, 95% CI: 2.38–39.47). It is associated with older (>75 years), advanced‐stage, platinum‐resistant patients, residual disease, and shorter PFS. In contrast, Class 2 is linked to platinum sensitivity, higher complete response rates (RECIST), and better prognosis but shows no correlation with CA‐125. These findings highlight PLAT‐M8's potential in guiding second‐line chemotherapy decisions. The PLAT‐M8 methylation biomarker is associated with survival in relapsed OC patients and may potentially predict their response to second‐line platinum treatment.

Epigenetic mechanisms of PARP inhibitor resistance in ovarian cancer: A systematic review with bioinformatic analysis of clinically actionable genes

PARP inhibitors (PARPi) improve ovarian cancer (OC) outcomes, but resistance remains a major challenge without reliable prognostic biomarkers. This study identified epigenetic hallmarks of PARPi resistance by integrating 27 studies (22 preclinical, 5 clinical) from the past 15 years, and validating candidate genes using web-based bioinformatics tools and public microarray/RNA-seq datasets from non-relapsed, primary OC tissues. We hypothesised that early aberrant expression of these epigenetically altered, PARPi resistance-related genes in tumours may be linked to disease progression (PFS) and could serve as early biomarkers to be associated with PARPi resistance during first-line treatment. We confirmed epigenetic involvement in PARPi resistance across 36 genes linked to epigenetic modifications. Of these, 10 genes (n = 614-1435)-including RNASEH2B (HR=1.41), VHL (HR=1.26), ATM (HR=1.22), XRCC1 (HR=1.20), NRP1 (HR=1.16), KAT2B (HR=1.16), EZH2 (HR=1.15), CREBBP (HR=1.14), FZD10 (HR=0.87), and CARM1 (HR=0.86)-showed significant prognostic value for PFS (all: p < 0.05). This 10-gene signature remained collectively significant (HR 1.27, p = 0.014). RNA-seq validation showed differential expression of these genes, with highest fold-change overexpression in tumours for FZD10 (4.20), EZH2 (3.56), and CARM1 (1.61), and lowest in ATM (0.22), KAT2B (0.33), and NRP1 (0.44). GO and KEGG analyses revealed these genes are enriched in key resistance pathways, including impaired DNA repair, reduced replication stress, immune evasion, and stemness maintenance. This review with bioinformatic validation identified a 10-gene epigenetic signature associated with PARPi resistance and disease progression. These clinically actionable genes, aberrantly expressed before treatment, may serve as early biomarkers for risk stratification. Further validation in PARPi-sensitive and -resistant ovarian cancer cohorts is needed.

Exploring Knowledge, Attitudes, Practices, and Information-Seeking on HPV Infection and Cervical Cancer Prevention in Rural Indonesia

Cervical cancer remains a leading public health problem in Indonesia, with low screening and HPV vaccination coverage, particularly in rural areas where knowledge gaps and limited healthcare access persist. This study aims to assess the knowledge, attitudes, and practices (KAP) regarding HPV infection and cervical cancer, and the role of information-seeking behavior in identifying effective channels for raising awareness on these issues. A cross-sectional study was conducted between 20 March 2023 and 20 January 2024, involving 220 women from two rural districts in North Moluccas, selected via convenience sampling. Data were collected using a validated questionnaire administered through face-to-face interviews. Data were analyzed using SPSS version 25.0 with descriptive statistics, normality testing (Kolmogorov-Smirnov), bivariate analyses (Chi-square, Fisher's Exact, Pearson's or Spearman's tests), and multivariate logistic regression (backward LR, p < 0.05), with model performance assessed using ROC curves and AUC values. Most participants demonstrated poor KAP, with 18.7% showing good knowledge, 22.7% expressing a positive attitude, and 44.5% engaging in favorable practices. KAP were found to be positively correlated (p<0.001). Key predictors of good knowledge included higher education (AOR = 7.07), family history of cancer (AOR = 15.20), private vehicle use (AOR = 4.15), and active health-information seeking behavior (HISB) (AOR = 3.41). Determinants for a positive attitude included higher education (AOR = 3.79), family history of cancer (AOR = 4.42), active HISB (AOR = 3.88), and good knowledge (OR = 10.29). Favorable practices were influenced by private vehicle use (AOR = 2.66) and positive attitude (AOR = 20.62). In conclusion, KAP are influenced by HISB, and involving healthcare workers in providing information, particularly through digital platforms, has the potential to improve KAP in rural communities.

Knowledge, attitudes, and practices among Indonesian urban communities regarding HPV infection, cervical cancer, and HPV vaccination

Background Few studies explored Indonesian understanding of cervical cancer (CC) and the human papillomavirus (HPV) vaccination. We aimed to investigate the association between knowledge, attitudes, and practices (KAP) and socio-demographical influences related to HPV, CC, and vaccination among Indonesian urban citizens. Methods We conducted an online survey during March 2020-August 2021 using the Snowball sampling technique. The socio-demographic characteristic and KAP responses were collected via Google Forms from 400 respondents in Jakarta. The knowledge and attitudes were divided into HPV and CC (aspect 1) and HPV vaccination (aspect 2). Correlation between KAP scores was performed using Spearman’s test, and multiple logistic regression analyses were conducted to determine KAP predictors. Results Indonesian urban citizens in Jakarta were found to have poor knowledge in individual aspects of the inquiry but moderate knowledge overall, good attitude in inquiry both in each aspect and overall, and unsatisfying practices. Overall, in the general population, men, and women respectively: 50.8%, 32.4%, and 53.6% had good knowledge; 82.0%, 75.2%, and 84.4% expressed positive attitude; and 30.3%, 15.2%, and 35.6% applied favorable practice regarding questions inquired. Knowledge was weakly correlated towards attitude (ρ = 0.385) but moderately correlated with practice (ρ = 0.485); attitude was moderately correlated with practice (ρ = 0.577), all results: p&lt;0.001. Significant odds ratio (OR) for predictors to good knowledge were female sex (OR = 2.99), higher education (OR = 2.91), and higher mother’s education (OR = 2.15). Factors related to positive attitudes were higher mother’s education (OR = 4.13), younger age (OR = 1.86), and better results in the knowledge inquiries (OR = 2.96). Factors that suggested better practices were female sex (OR = 2.33), being employed (OR = 1.68), excellent knowledge scores (OR = 4.56), and positive attitudes expressions (OR = 8.05). Having done one vaccination dose and intention to receive vaccines were significantly influenced by good KAP. Conclusions KAP had inter-association to successful CC and HPV prevention programs, and socio-demographical characteristics are critical to influencing better KAP.