A comprehensive study based on large-sample multi-omics integration and machine learning to decode mitochondria-associated genes: from digestive tract tumours to gastric cancer

Abstract

Background Mitochondria-related genes play a crucial role in driving tumour cell progression, but little is known about their molecular mechanisms and biological pathways. This study conducted a comprehensive analysis of the mitochondrial key gene LACTB2 in digestive tract tumours and explored a novel early blood-based diagnostic model for gastric cancer (GC). Methods This study analyzed LACTB2 expression, biological pathways, and immune regulation in a large cohort of 10,581 samples. IHC staining was performed using 236 internal GC samples. Multi-omics data were integrated for comprehensive analysis of LACTB2 in GC. A combination of extensive clinical samples and multiple machine learning models enabled the construction of prognostic and blood-based diagnostic models (n = 14,219). Results LACTB2 overexpression is associated with clinical metastasis and the activation of pro-cancer pathways, and LACTB2 may mediate immune suppression and immune evasion through various methods. There is a significant transcriptional regulatory network upstream of LACTB2. LACTB2 overexpression may drive malignant transformation of GC epithelial cells through pro-cancer metabolic signalling networks, and the related mechanisms were spatially validated. Dysregulated expression of LACTB2 can affect the prognosis of GC patients, and Afatinib and Ulixertinib may play a significant role in targeting LACTB2 in the treatment of GC patients. An excellent early blood diagnostic model for GC was constructed based on the upstream miRNA of LACTB2. Conclusion Our study provides new insights into the differential expression and pathogenesis of LACTB2 in digestive tract tumours, particularly its prognostic and diagnostic value in GC.