Biomarker Discovery for Early Detection of Esophageal Cancer in High-Risk Populations in the North Central Zone of Nigeria

Esophageal cancer carries an extremely poor prognosis in Nigeria, with nearly all cases diagnosed at unresectable stages due to the absence of symptom-based screening programs and early biomarker detection tools. A high-incidence cluster in the North Central zone has been anecdotally reported but not formally characterized. This dissertation conducts a biomarker discovery study for early esophageal cancer detection in high-risk populations in the North Central geopolitical zone of Nigeria. A case-control design recruited 80 histologically confirmed esophageal cancer cases and 160 high-risk cancer-free controls from Benue, Kogi, and Nasarawa states between 2020 to 2024. Serum samples underwent unbiased proteomics screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Candidate biomarkers were validated by ELISA in the full cohort. Epidemiological risk profiling including dietary nitrosamine exposure and alcohol use was conducted in parallel. LC-MS/MS identified 24 differentially expressed proteins in cancer cases versus controls. A three-protein biomarker panel (including upregulated fibronectin 1, VEGF-A, and complement C3) achieved an AUC of 0.88 in the validation cohort for early-stage esophageal cancer detection. Nitrosamine-rich fermented food consumption and high-volume alcohol use were strongly correlated with cancer incidence in this zone. The dissertation provides original biomarker data and recommends a funded Phase II validation trial and community dietary intervention program in high-risk North Central communities. Keywords: esophageal cancer, biomarker, proteomics, North Central Nigeria, early detection