Integrated Multi-Omics Characterisation of Metabolic Reprogramming in Hepatocellular Carcinoma in Nigerian Patients

Hepatocellular carcinoma is the most prevalent liver malignancy in Nigeria and is strongly associated with hepatitis B virus infection and aflatoxin B1 exposure, yet the multi-omics landscape of metabolic reprogramming in Nigerian hepatocellular carcinoma patients has not been characterized, limiting the development of locally relevant biomarkers and therapeutic targets. This dissertation presents an integrated multi-omics characterisation of metabolic reprogramming in hepatocellular carcinoma using tumour and matched non-tumour tissue from Nigerian patients at three southern Nigerian tertiary hospitals. Tissue specimens were collected from forty hepatocellular carcinoma patients and subjected to transcriptomics by RNA-sequencing, proteomics by TMT-labelled tandem mass spectrometry, and metabolomics by liquid chromatography-mass spectrometry. Bioinformatic integration by multi-omics factor analysis and network-based approaches identified key metabolic nodes coordinately dysregulated at transcript, protein, and metabolite levels. Key findings include transcriptional upregulation of pentose phosphate pathway enzymes and fatty acid synthesis machinery alongside profound downregulation of mitochondrial beta-oxidation enzymes, consistent with the Warburg effect but with a distinctive fatty acid synthesis emphasis not previously reported as dominant in hepatocellular carcinoma from this geographical context. Aflatoxin B1-associated adducts in tumour tissue correlated with specific TP53 mutation signatures and with a distinct metabolic subgroup characterised by elevated sphingolipid biosynthesis. Integrated proteometabolomic analysis identified elevated glycine-serine metabolism and one-carbon cycle flux as a metabolic hallmark of the rapidly proliferating tumour subgroup. The dissertation constructs an original metabolic reprogramming model specific to Nigerian hepatocellular carcinoma that distinguishes hepatitis B-dominant from aflatoxin-dominant molecular subtypes. Keywords: hepatocellular carcinoma, multi-omics, metabolic reprogramming, Warburg effect, Nigeria.