APEX1 as a novel diagnostic and prognostic biomarker for hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the sixth prevailing cancer globally and is the second greatest reason for cancer-linked deaths in males, surpassed only by lung cancer. A significant number of HCC cases experiencing advanced stages are due to the frequent absence or inconspicuousness of early symptoms. Consequently, discovering reliable early diagnostic indicators and innovative treatment targets is essential to improve survival and overall outcomes for HCC patients. Herein, we aimed to evaluate the diagnostic potential of APEX1 in Egyptian HCC patients and explore its prognostic significance before treatment initiation. Study design and methodology: This research was conducted as a prospective comparative cohort study involving 60 Egyptian participants, age range more than 18 years selected from internal medicine and hepatology outpatient clinics and inpatient wards at Ain Shams University hospitals from January 2024 to July 2024, after informed consent was taken from the patients, who were allocated into: Group A (Cirrhotic) comprising 12 liver cirrhosis patients but without HCC, acting as the control group; Group B (HCC) included 48 patients diagnosed with HCC. Group B was further subdivided into four subgroups: Subgroup 1: 12 patients receiving palliative (supportive) care; Subgroup 2: 12 patients treated with Sorafenib, Subgroup 3: 12 patients treated with trans-arterial chemoembolization (TACE); and Subgroup 4: 12 patients treated with radiofrequency ablation (RFA). Data collection included anthropometric measurements, laboratory tests, radiological findings, CHILD-PUGH scores, BCLC scores, and patient performance metrics, gathered both before and after treatment. The data were analyzed utilizing IBM SPSS (ver. 27). Results: The study identified a serum APEX1 level cutoff of >13.72 ng/mL as a biomarker to differentiate between cirrhotic patients and those with HCC (sensitivity = 92.31%, specificity = 100.0%). The threshold for AFP was 20 ng/mL (sensitivity = 76.92%, specificity = 100.0%). Notably, significant differences in AFP and APEX1 levels were found between cirrhotic patients and HCC patients in the RF and TACE subgroups at baseline (p-value 0.004, < 0.001 for AFP and APEX1, respectively), indicating that APEX1 may serve as a more sensitive biomarker for early HCC detection. Both AFP and APEX1 exhibited a positive predictive value (PPV) of 100%. Furthermore, the study revealed that an AFP level exceeding 280 ng/mL at baseline could predict a poor prognosis (sensitivity = 57.1%, specificity = 81.8%, AUC = 0.679). In contrast, an APEX1 level greater than 9.96 ng/mL at baseline was found to be a noteworthy predictor of poor prognosis (specificity = 86.4%, sensitivity = 92.9%, AUC = 0.857). Conclusions : - APEX1 has proven to be a more sensitive and accurate serum biomarker than AFP for diagnosing HCC. - Serum APEX1 levels revealed a significant rise in HCC patients, even during the early stages (candidates for radiological/therapeutic intervention), making it a valuable tool for screening and early detection in surveillance programs. - APEX1 demonstrated the ability to predict patient prognosis even prior to the initiation of treatment.