Multiple myeloma (MM) is highly heterogenous and dynamic in its genomic abnormalities. Capturing a representative image of these alterations is essential in understanding the molecular pathogenesis and progression of the disease but was limited by single-site invasive bone marrow (BM) biopsy-based genomics studies. We compared the mutational landscapes of circulating tumor DNA (ctDNA) and BM in 82 patients with newly diagnosed MM. A 413-gene panel was used in the sequencing. Our results showed that more than 70% of MM patients showed one or more genes with somatic mutations and at least half of the mutated genes were shared between ctDNA and BM samples. Compared to the BM samples, ctDNA exhibited more types of driver mutations in the shared driver genes, higher numbers of uniquely mutated genes and subclonal clusters, more translocation-associated mutations, and higher frequencies of mutated genes enriched in the transcriptional regulation pathway. Multivariate Cox analysis showed that age, ctDNA mutations in the transcriptional regulation pathway and DNA repair pathway were independent predictors of progression-free survival (PFS). Our results demonstrated sequencing of ctDNA provides more thorough information on the genomic instability and is a potential representative biomarker for risk stratification and in newly diagnosed MM than bone marrow.

Objectives: Circulating tumor DNA (ctDNA) has emerged as a reliable prognostic biomarker in both early- and late-stage non-small cell lung cancer (NSCLC) patients. However, its role in NSCLC with pleural dissemination (M1a), a subset of disease with indolent biology, remains to be elucidated. Methods: We collected 41 M1a patients with serial ctDNA and CEA monitoring. Progression-free survival (PFS) was assessed between patients with different levels of ctDNA and CEA. An independent cohort of 61 M1a patients was included for validation. Results: At the diagnostic landmark, the detection rates for ctDNA and CEA were 22% and 55%, respectively. Among patients who experienced disease progression with pleural metastases, only ten had detectable ctDNA in longitudinal timepoints, resulting in a sensitivity of 50%. Moreover, there was no significant difference in PFS between patients with longitudinally detectable and undetectable ctDNA (HR: 0.86, 95% CI 0.33–2.23, p = 0.76). In contrast, patients with a decreasing CEA trend within 3 months after diagnosis were associated with an improved PFS (HR: 0.22; 95% CI, 0.03–1.48, p = 0.004). This finding is confirmed in an independent M1a patient cohort. Conclusions: Together, our findings suggest that M1a NSCLC with isolated pleural dissemination may represent a “non-shedding” tumor type, where ctDNA shows limited diagnostic and prognostic value. Monitoring early changes in CEA could be a more cost-effective predictor of disease progression.

To establish a cuproptosis-related lncRNA signature and evaluate its prognostic value and potential immunological relevance in gastric cancer (GC). Transcriptomic data from the cancer genome atlas and gene expression omnibus were analyzed using Pearson correlation and least absolute shrinkage and selection operator Cox regression to construct the prognostic model. Model performance was assessed by Kaplan–Meier analysis, time-dependent receiver operating characteristic curves, and decision curve analysis. An mRNA-based RS score was further validated in Gene Expression Omnibus datasets and the IMvigor210 cohort. Expression of 2 key long noncoding RNAs (AC245041.1 and LINC01614) was confirmed by qRT-PCR in an independent GC cohort. A 25-lncRNA cuproptosis-related signature effectively stratified patients into high- and low-risk groups, with the high-risk group showing significantly poorer survival. The model outperformed conventional clinical variables. Functional enrichment suggested involvement of immune regulation and mitochondrial pathways related to cuproptosis, and the low-risk group displayed a more immunologically active profile. The RS score showed consistent predictive performance across external cohorts, and qRT-PCR validated the prognostic relevance of AC245041.1 and LINC01614. This cuproptosis-related lncRNA signature demonstrates potential as a prognostic indicator and may provide insights into immunotherapy relevance, offering a promising direction for personalized GC management.