Transl Oncol. 2026 Jan 6;64:102660. doi: 10.1016/j.tranon.2025.102660. Online ahead of print.

ABSTRACT

Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult metastases limit the survival benefits of conventional treatments. The current TNM staging system fails to fully reflect tumor heterogeneity or the dynamic molecular evolution of the disease, thus affecting the prediction of recurrence and the prognostic stratification. Some recent advances in minimal residual disease (MRD) detection, such as ultra-sensitive liquid biopsy technologies, have largely overcome the limitations of traditional imaging and offered a transformative approach for continuous, precision-based management of lung cancer. This review systematically summarized the technological evolution of MRD detection and highlighted its clinical significance in guiding adaptive therapy for NSCLC, including treatment escalation, de-escalation, and the emerging concept of precision-guided drug holidays. Moreover, the authors comprehensively discussed the "Four-Dimensional TNMB Staging System," which incorporates continuous molecular monitoring to address the static limitations of conventional staging and enhance the accuracy of prognostic stratification. Although ongoing challenges, such as the lack of standardized interpretation criteria and limited detection sensitivity, the combinations with the third-generation liquid biopsy platforms, multi-omics analyses, and multi-center prospective validation studies are expected to advance the clinical implementation of MRD-guided strategies. The paradigm change will enable the transition of NSCLC management from conventional standardized models to a precision-guided, closed-loop system of "monitoring-intervention-remonitoring," establishing a solid theoretical and practical foundation for comprehensive, molecularly driven management strategies.

PMID:41496417 | DOI:10.1016/j.tranon.2025.102660

FASEB J. 2025 Aug 31;39(16):e70978. doi: 10.1096/fj.202500722RR.

ABSTRACT

Ribophorin 1 (RPN1), a key component of the oligosaccharyltransferase complex, is implicated in tumor progression through glycosylation-mediated pathways, yet its pan-cancer roles remain unexplored. This study presents a comprehensive multi-omics analysis of RPN1 across 33 cancers such as sarcoma (SARC), integrating genomic, transcriptomic, and proteomic data from TCGA, GTEx, and CPTAC. RPN1 was significantly overexpressed in 14 malignancies and correlated with advanced tumor stages and poor prognosis in glioblastoma (GBM), lower-grade glioma, SARC and hepatocellular carcinoma, validated in an independent glioma cohort (n = 151). Genomically, RPN1 amplification linked to homologous recombination deficiency and elevated tumor mutational burden, suggesting a role in genomic instability. Critically, multiplex immunofluorescence demonstrates RPN1 overexpression colocalizes with CD206⁺ M2 macrophages in tumor microenvironments, while in vitro coculture experiments confirm RPN1-dependent microglial recruitment and M2 polarization. RPN1 expression negatively correlates with CD8⁺ T cell infiltration and predicts resistance to chemotherapy (GBM, ovarian cancer) and immunotherapy (GBM, esophageal carcinoma), though it associates with PD-1 inhibitor sensitivity in bladder cancer. Functional validation shows RPN1 knockdown suppresses proliferation, migration, and invasion in GBM cells. Pathway enrichment connects RPN1 to endoplasmic reticulum stress, glycosylation, DNA repair, and immune checkpoint regulation. These findings position RPN1 as a multimodal oncogenic driver promoting genomic instability, immunosuppressive microenvironment remodeling, and context-dependent therapeutic vulnerabilities across cancers.

PMID:40857034 | DOI:10.1096/fj.202500722RR