METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.
RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.
DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.
METHODS AND RESULTS: We analyzed the gene expression patterns on 238 fresh-frozen samples, comparing tumors with their normal adjacent tissues (NATs). HNSCC samples showed higher PCAT-1 and FSCN-1 expression compared to NATs (p
PRINCIPAL FINDINGS: Relevant published literature was identified by searching major electronic databases using targeted search queries. This process retrieved a total of 81 peer-reviewed research articles deemed eligible for inclusion, as they partially or fully met the pre-defined selection criteria. These eligible articles underwent a qualitative synthesis and were included in the scoping review. Within these, 11 studies specifically explored Ov-CCA tissues to investigate potential epigenetic biomarkers and therapeutic targets. This subset of 11 articles provided a foundation for exploring the applications of epigenetics-based therapies and biomarkers for Ov-CCA. These articles delved into various epigenetic modifications, including DNA methylation and histone modifications, and examined genes with aberrant epigenetic changes linked to deregulated signalling pathways in Ov-CCA progression.
CONCLUSIONS: This review identified epigenetic changes and Wnt/β-catenin pathway deregulation as key drivers in Ov-CCA pathogenesis. Promoter hypermethylation of specific genes suggests potential diagnostic biomarkers and dysregulation of Wnt/β-catenin-modulating genes contributes to pathway activation in Ov-CCA progression. Reversible epigenetic changes offer opportunities for dynamic disease monitoring and targeted interventions. Therefore, this study underscores the importance of these epigenetic modifications in Ov-CCA development, suggesting novel therapeutic targets within disrupted signalling networks. However, additional validation is crucial for translating these novel insights into clinically applicable strategies, enhancing personalised Ov-CCA management approaches.
METHODS: 240 HER2-positive MBC patients from 2004 to 2015 were retrieved from the surveillance, epidemiology, and end results (SEER) database. All HER2-positive MBC patients were divided randomly into training (n = 144) and validation cohorts (n = 96) according to a ratio of 6:4. Univariate and multivariate Cox regression analyses were used to determine the prognostic factors associated with HER2-positive MBC patients. A clinical prediction model was constructed to predict the overall survival of these patients. The nomogram model was assessed by using receiver operating characteristics (ROC) curves, calibration plots and decision curve analysis (DCA).
RESULTS: The Cox regression analysis showed that T-stage, M-stage, surgery and chemotherapy were independent risk factors for the prognosis of HER2-positive MBC patients. The model could also accurately predict the Overall survival (OS) of the patients. In the training and validation cohorts, the C indexes of the OS nomograms were 0.746 (0.677-0.815) and 0.754 (0.679-0.829), respectively. Calibration curves and DCA verified the reliability and accuracy of the clinical prediction model.
CONCLUSION: In conclusion, the predictive model constructed had good clinical utility and can help the clinician to select appropriate treatment strategies for HER2-positive MBC patients.
MATERIALS AND METHODS: 300 healthy women were recruited comprising 150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to a pelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levels were determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The reference intervals were determined following CLSI guidelines (C28-A2) using a non-parametric method.
RESULTS: The upper limits of the 95th percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L, and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was noted to increase with age especially in women who were more than 50 years old. We also noted that our proposed reference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study also showed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels of HE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between the Malays and Chinese ethnic groups.
CONCLUSIONS: More data are needed to establish a reference interval that will better represent the multiethnic Malaysian population. Probably a larger sampling size of equal representation of the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidence on whether genetics plays a role in reference interval determination.