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.

Red blood cells (RBC) are commonly known as cells with no nucleus or mitochondria and are assumed to be a transportation vehicle. This study confirms that RBC contain long DNA fragments inside with stain by both microscope and flow cytometry, which covers most nuclear and mitochondrial genome regions by next‐generation sequencing (NGS). Such characteristics demonstrate a significant difference compared with A549 cell line or paired peripheral blood mononuclear cell as nucleated cells. To further explore the characteristics of RNA DNA, DNA from 20 RBC samples is sequenced by NGS. Interestingly, several gaps and multiple regions with copy number variation are observed significantly different between different samples, which could be used to distinguish samples with different health status accurately. Using an in vitro co‐culture system, it is shown that RBC could absorb DNA‐bearing tumorigenic mutations from cancer cell lines but requires cell‐to‐cell contact. Finally, based on a small scale clinical trial, it is confirmed that common genetic mutations of cancer tissues could be detected in RBC from patients with early‐stage non‐small‐cell lung cancer. This study highlights a new biological phenomenon involving RBC and its translational potential as a novel liquid biopsy technology platform for early cancer screening and diagnosis of malignancy.

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.