Diagnosis of malignant body fluids via cancer-universal methylation in cell-free DNA.

BACKGROUNDDifferentiating malignant from nonmalignant body fluids remains a clinical challenge because of the unsatisfying performance of conventional cytology. We aimed to improve the sensitivity and ubiquity of cancer cell detection by assaying universal cancer-only methylation (UCOM) markers in supernatant cell-free DNA (cfDNA).METHODSAn observational prospective cohort including 1,321 nonmalignant and malignant body fluids of multiple cancers was used to develop and validate a cfDNA UCOM methylation diagnostic assay. All samples were divided into 2 portions for cytology and supernatant cfDNA methylation analysis.RESULTSThe significant hypermethylation of a potentially novel UCOM marker, TAGMe, together with the formerly reported PCDHGB7, was identified in the cfDNA of malignant body fluid samples. The combined model, cell-free cancer-universal methylation (CUE), was developed and validated in a prospective multicancer cohort with markedly elevated sensitivity and specificity, and was further verified in a set containing additional types of malignant body fluids and metastases. In addition, it remained hypersensitive in detecting cancer cells in cytologically negative malignant samples.CONCLUSIONcfDNA methylation markers are robust in detecting tumor cells and are applicable to diverse body fluids and tumor types, providing a feasible complement to current cytology-based diagnostic analyses.TRIAL REGISTRATIONThis study was registered at Chictr.org.cn (ChiCTR2200060532).FUNDINGNational Natural Science Foundation of China (32270645, 31872814, 32000505, 82170088), the National Key R&D Program of Ningxia Hui Autonomous region (2022BEG01003), Shanghai Municipal Key Clinical Specialty (shslczdzk02201), Science and Technology Commission of Shanghai Municipality (20DZ2261200, 20DZ2254400), and Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101).

The outpost against cancer: universal cancer only markers.

Cancer is the leading cause of death worldwide. Early detection of cancer can lower the mortality of all types of cancer; however, effective early-detection biomarkers are lacking for most types of cancers. DNA methylation has always been a major target of interest because DNA methylation usually occurs before other detectable genetic changes. While investigating the common features of cancer using a novel guide positioning sequencing for DNA methylation, a series of universal cancer only markers (UCOMs) have emerged as strong candidates for effective and accurate early detection of cancer. While the clinical value of current cancer biomarkers is diminished by low sensitivity and/or low specificity, the unique characteristics of UCOMs ensure clinically meaningful results. Validation of the clinical potential of UCOMs in lung, cervical, endometrial, and urothelial cancers further supports the application of UCOMs in multiple cancer types and various clinical scenarios. In fact, the applications of UCOMs are currently under active investigation with further evaluation in the early detection of cancer, auxiliary diagnosis, treatment efficacy, and recurrence monitoring. The molecular mechanisms by which UCOMs detect cancers are the next important topics to be investigated. The application of UCOMs in real-world scenarios also requires implementation and refinement.

Pre-enriched saline gargle samples for detection of SARS-CoV-2.

A self­collected gargle sample, which avoids discomfort and largely reduces the dependency on medical resources, is emerging for detection of SARS­CoV­2. However, the incomplete usage of starting materials for both routine oropharyngeal swabs (OPS)/nasopharyngeal swabs (NPS) and saline gargle (SG) samples implies sensitivity can be further improved. Presented here is a bead­based strategy for pre­enrichment of SG samples, and results revealed that it acquired about 20 times the starting materials obtained from OPS samples for downstream detection of SARS­CoV­2. The sensitivity and specificity of this pre­enrichment strategy were validated in 100 paired pre­enriched saline gargle (PenSG) and OPS samples and 89 PenSG samples from healthy volunteers. In addition to detection of SARS­CoV­2, this pre­enrichment strategy may also be implemented in more clinical settings to optimize detection of other diseases.