128 Metabolic Reprogramming and ACACB Expression in Cancer: Insights into Fatty Acid Synthesis

Abstract

Abstract Aim This study investigates the expression of acetyl-CoA carboxylase beta (ACACB) in metabolically reprogrammed cancers—clear cell renal cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), breast carcinoma (BRCA), lung squamous carcinoma (LUSC), lung adenocarcinoma (LUAD), and bladder urothelial carcinoma (BLCA)—compared to non-reprogrammed chromophobe renal cell carcinoma (KICH), to understand its role in cancer metabolism. Method ACACB expression data were analyzed using TCGA databases (TIMER 2.0, GEPIA 2.0, UALCAN). Sample sizes included: KIRC (533 tumors, 72 normal), LIHC (371 tumors, 50 normal), BRCA (1,093 tumors, 112 normal), BLCA (408 tumors, 19 normal), LUSC (501 tumors, 51 normal), LUAD (515 tumors, 59 normal), and KICH (66 tumors, 25 normal). Statistical significance was set at p < 0.05. Validation was performed using NCBI GEO datasets: GSE15641 (32 KIRC, 6 KICH, 33 normal), GSE41804 (20 LIHC tumor, 20 normal), GSE40275 (4 LUSC, 8 LUAD, 43 normal), GSE42089 (10 BLCA tumor, 7 normal), and GSE22820 (176 BRCA tumor, 20 normal). Statistical significance was determined using adjusted p-values (< 0.05) and fold-change thresholds (|Log2FC| > 0.84). Results ACACB was significantly downregulated in reprogrammed cancers (KIRC, LIHC, BRCA, LUSC, LUAD, BLCA) compared to normal tissues (p < 0.05), while it was upregulated in non-reprogrammed KICH using TIMER 2.0, GEPIA and UALCAN . NCBI GEO datasets confirmed these findings. Conclusions This study underscores the reduced expression of ACACB in metabolically reprogrammed cancers, suggesting a shift away from fatty acid synthesis. This shift highlights the metabolic adaptations of cancer cells, where fatty acid production becomes less prioritized.