Pan-Cancer Expression Analysis of the Aminoadipate-semialdehyde synthase (AASS) Gene: Insights into its Potential Role in Oncogenic Metabolic Reprogramming

Background Metabolic reprogramming is a hallmark of cancer, yet the role of AASS, the rate-limiting enzyme in lysine degradation, remains uncharacterized in a pan-cancer context. This study aimed to define the expression, prognostic significance, and functional network of AASS across human malignancies. Methods A comprehensive bioinformatic analysis was performed using transcriptomic and clinical data from 33 cancer types in The Cancer Genome Atlas (TCGA). The investigation included differential expression analysis, survival modelling, and construction of co-expression networks. Results AASS expression was highly heterogeneous. It was significantly upregulated in Kidney Renal Clear Cell Carcinoma (KIRC; p < 0.001) and downregulated in Liver Hepatocellular Carcinoma (LIHC; p < 0.001). High AASS expression correlated with favorable patient survival in both KIRC and LIHC (p < 0.001) but with an unfavorable prognosis in Lung Squamous Cell Carcinoma (LUSC; p = 0.015). Functional enrichment revealed that AASS co-expresses with genes central to mitochondrial and catabolic processes, including fatty acid oxidation. Conclusion AASS is a context-dependent metabolic modulator whose prognostic impact is dictated by the specific tumor type. These findings establish AASS as a novel, clinically relevant biomarker and a potential therapeutic target in specific cancers.