A Novel MPT-Driven Necrosis-Related lncRNA Signature for Prognostic Prediction in Hepatocellular Carcinoma: Validation Using Organoids.

[BACKGROUND] Mitochondrial permeability transition (MPT)-driven necrosis, a recently identified form of programmed cell death, significantly influences tumor progression, therapy response, and prognosis. However, research on mitochondrial permeability transition-driven necrosis-related long non-coding ribonucleic acids (MPTDNRlncRNAs) in hepatocellular carcinoma (HCC) remains limited.

[METHODS] In the current study, we aimed to construct an MPTDNRlncRNA signature to predict survival and classify patients with HCC. RNA sequencing and clinical data were sourced from the Cancer Genome Atlas database, while MPT-driven necrosis-linked genes were obtained from the Gene Set Enrichment Analysis database. We identified MPTDNRlncRNAs in HCC tumor tissues and deployed the least absolute shrinkage and selection operator-Cox analysis to construct a predictive lncRNA signature. Immune cell infiltration variations were analyzed between high- and low-risk subgroups. The MPTDNRlncRNA signature performance was estimated using statistical methodologies, and bioinformatics methods were utilized to investigate functional and pathway differences across risk groups.

[RESULTS] A seven-lncRNA signature specific to HCC was developed, and its predictive accuracy was systematically evaluated using survival analysis, time-dependent receiver operating characteristic curves, and Cox regression analyses. Correlation analysis demonstrated a strong association between the lncRNA signature and immune cell infiltration, several immune checkpoint targets, and its significant prognostic value for patients with HCC. Additionally, LINC02313 was recognized as a hub lncRNA in vitro, demonstrating its role in promoting cell proliferation and tumor metastasis. Finally, we validated the function of LINC02313 using a liver cancer organoid model.

[CONCLUSION] The effective construction of an MPT-driven necrosis-related prognostic model highlights its potential to independently predict the prognosis of patients with HCC. These findings not only deepen our understanding of MPT-driven necrosis but also offer novel theoretical foundations for developing more effective treatment strategies. The gene LINC02313 has been identified as a promoter of HCC's ability to proliferate and invade, underscoring its potential as a therapeutic target for HCC.