ArticleBMC cancer2026
Characterizing prognostic and immunological traits of kidney renal clear cell carcinoma via mitochondria-associated membranes and identifying DNM1L as a potential therapeutic target using machine learning.
Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMitochondrial-associated membranes (MAMs) participate in cellular metabolism, calcium signaling, and cancer reprogramming, but their role in kidney renal clear cell carcinoma (KIRC) remains unclear.
methodsClinical/transcriptomic data of KIRC and previously reported MAMs-related genes were obtained from TCGA, E-MTAB-1980, and GSE29609. After analyzing MAMs gene expression in KIRC, 101 models were generated via 10 machine learning algorithms to select the optimal MAMs-based scoring system. Survival (Kaplan-Meier) and Cox regression analyses evaluated its prognostic value; associations with immune cell infiltration, checkpoints, and drug sensitivity were explored, and key genes were validated in vitro and in vivo.
resultsForty-two MAMs-related genes were identified, most highly expressed in KIRC tissues. A 9-gene MAMs scoring system was built using the Stepwise Cox model. High-score patients had worse prognosis, and the system was an independent prognostic factor for KIRC. High scores correlated with advanced TNM stage/grade, elevated CTLA4/PD1 (better immunotherapy response in CTLA4+/PD1+ subgroups), and sensitivity to temsirolimus/sunitinib (low scores sensitive to sorafenib). DNM1L was a key gene; its knockdown inhibited KIRC cell proliferation, invasion, and migration in vitro. In vivo experiments further confirmed that DNM1L knockdown suppressed tumor growth in BALB/c nude mice bearing KIRC xenografts.
conclusionThis study identified high MAMs-related gene expression in KIRC, developed a 9-gene MAMs scoring system, and validated DNM1L as a key gene, providing new insights into KIRC prognostic biomarkers and therapeutic targets.
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