Cutaneous melanoma (CM) is a life-threatening form of skin cancer. Prognostic biomarkers can reliably stratify patients at initial melanoma diagnosis according to risk, and may inform clinical decisions. Here, we performed a retrospective, cohort-based study analyzing genome-wide DNA methylation of 461 patients with CM from the TCGA database. Cox regression analyses were conducted to establish a four-DNA methylation signature that was significantly associated with the overall survival (OS) of patients with CM, and that was validated in an independent cohort. Corresponding Kaplan–Meier analysis displayed a distinct separation in OS. The ROC analysis confirmed that the predictive signature performed well. Notably, this signature exhibited much higher predictive accuracy in comparison with known biomarkers. This signature was significantly correlated with immune checkpoint blockade (ICB) immunotherapy-related signatures, and may have potential as a guide for measures of responsiveness to ICB immunotherapy.
Ovarian cancer is the most fatal tumor of the female reproductive system and the fifth leading cause of cancer death among women in the USA. The prognosis is poor due to the lack of biomarkers for treatment options. The methylation array data of 551 patients with ovarian serous cystadenocarcinoma (OSC) in The Cancer Genome Atlas (TCGA) database were assessed in this study to explore the methylation biomarkers associated with prognosis and improve the prognosis of patients. These patients were divided into training (first two thirds) and validation datasets (remaining one third). A five-DNA methylation signature was found to be significantly associated with the overall survival of patients with OSC using the Cox regression analysis in the training dataset. The Kaplan–Meier analysis showed that the five-DNA methylation signature could significantly distinguish the high- and low-risk patients in both training and validation sets. The receiver operating characteristic (ROC) analysis further confirmed that the five-DNA methylation signature exhibited high sensitivity and specificity to predict the prognostic survival of patients. Also, the five-DNA methylation signature was not only applicable in patients of different ages, stages, histologic grade, and size of residual tumor after surgery but also more accurate in predicting OSC prognosis compared with known biomarkers. This five-DNA methylation signature demonstrated the potential of being a novel independent prognostic indicator and served as an important tool for guiding the clinical treatment of OSC to improve outcome prediction and management for patients. Hence, the findings of this study might have potential clinical significance.
3 November 2020 in Computational and Mathematical Methods in Medicine
Growing evidence suggests that the superiority of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) could act as biomarkers for cancer prognosis. However, the prognostic marker for hepatocellular carcinoma with high accuracy and sensitivity is still lacking. In this research, a retrospective, cohort-based study of genome-wide RNA-seq data of patients with hepatocellular carcinoma was carried out, and two protein-coding genes (GTPBP4, TREM-1) and one lncRNA (LINC00426) were sorted out to construct an integrative signature to predict the prognosis of patients. The results show that both the AUC and the C-index of this model perform well in TCGA validation dataset, cross-platform GEO validation dataset, and different subsets divided by gender, stage, and grade. The expression pattern and functional analysis show that all three genes contained in the model are associated with immune infiltration, cell proliferation, invasion, and metastasis, providing further confirmation of this model. In summary, the proposed model can effectively distinguish the high- and low-risk groups of hepatocellular carcinoma patients and is expected to shed light on the treatment of hepatocellular carcinoma and greatly improve the patients’ prognosis.
Cutaneous melanoma (CM) is one of the most aggressive skin tumors with a poor prognosis. Ferroptosis is a newly discovered form of regulated cell death that is closely associated with cancer development and immunotherapy. The aim of this study was to establish and validate a ferroptosis-related gene (FRG) DNA methylation signature to predict the prognosis of CM patients using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. A reliable four-FRG DNA methylation prognostic signature was constructed via Cox regression analysis based on TCGA database. Kaplan–Meier analysis showed that patients in the high-risk group tended to have a shorter overall survival (OS) than the low-risk group in both training TCGA and validation GEO cohorts. Time-dependent receiver operating characteristic (ROC) analysis showed the areas under the curve (AUC) at 1, 3, and 5 years were 0.738, 0.730, and 0.770 in TCGA cohort and 0.773, 0.775, and 0.905 in the validation cohort, respectively. Univariate and multivariate Cox regression analyses indicated that the signature was an independent prognostic indicator of OS in patients with CM. Immunogenomic profiling showed the low-risk group of patients had a higher immunophenoscore, and most immune checkpoints were negatively associated with the risk signature. Functional enrichment analysis revealed that immune response and immune-related pathways were enriched in the low-risk group. In conclusion, we established and validated a four-FRG DNA methylation signature that independently predicts prognosis in CM patients. This signature was strongly correlated with the immune landscape, and may serve as a biomarker to guide clinicians in making more precise and personalized treatment decisions for CM patients.
Background Bladder cancer is one of the most common cancers, and its histopathological type is mainly bladder urothelial carcinoma, accounting for about 90%. The prognostic biomarkers of bladder cancer are classified into clinical features biomarkers and molecular biomarkers. Nevertheless, due to the existence of individual specificity, patients with similar pathological characteristics still have great differences in the risk of disease recurrence. Therefore, it is often inaccurate to predict the survival status of patients based on clinical characteristic biomarkers, and a prognostic molecular biomarker that can grade the risk of bladder cancer patients is needed. Methods A total of three bladder urothelial carcinoma datasets were used in this study from the Cancer Genome Atlas database and Gene Expression Omnibus database. In order to avoid overfitting, all samples were randomly divided into one training set and three validation sets, which were used to construct and test the prognostic biomarker model of bladder urothelial carcinoma. Univariate and multivariate Cox regression were used to screen candidate mRNAs and construct prognostic biomarkers model. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model. Results A prognostic biomarker model of bladder urothelial carcinoma combining with eight mRNA was constructed. Kaplan–Meier analyses indicated that a significant difference in the survival time of patients between the high-risk and the low-risk group. The area under the ROC curve were 0.632 (95% confidence interval (CI) [0.541–0.723]), 0.693 (95% CI [0.601–0.784]) and 0.686 (95% CI [0.540–0.831]) when the model was used to predict the patient’s survival time in three validation datasets. The model showed high accuracy and applicability.
The prognosis for Cutaneous Melanoma (CM), a skin malignant tumor that is extremely aggressive, is not good. A recently identified type of controlled cell death that is intimately related to immunotherapy and the development of cancer is called cuproptosis. Using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we developed and validated a DNA-methylation located in cuproptosis death-related gene prognostic signature (CRG-located DNA-methylation prognostic signature) to predict CM’s prognosis. Kaplan–Meier analysis of our TCGA and GEO cohorts showed that high-risk patients had a shorter overall survival. The area under the curve (AUC) for the TCGA cohort was 0.742, while for the GEO cohort it was 0.733, according to the receiver operating characteristic (ROC) analysis. Furthermore, this signature was discovered as an independent prognostic indicator over CM patients based on Cox-regression analysis. Immunogenomic profiling indicated that majority immune-checkpoints got an opposite relationship with the signature, and patients in the group at low risk got higher immunophenoscore. Several immune pathways were enriched, according to functional enrichment analysis. In conclusion, a prognostic methylation signature for CM patients was established and confirmed. Because of its close relationship to the immune landscape, this signature may help clinicians make more accurate and individualized choices regarding therapy.