Hepatocellular cancer

Hepatocellular carcinoma (HCC) is the most common form of liver cancer (Llovet JM et al. (2021)) and the sixteenth most common leading cause of death worldwide (Asrani SK et al. (2019)). Its causes include hepatitis B or C infections, and liver cirrhosis, with 80-90% of all cases stemming from the latter. A higher incidence of cirrhosis has been associated with comorbidities such as chronic substance abuse, obesity, and diabetes (Matsushita H et al. (2019)). Thus, preventative strategies include hepatitis B vaccines, anti-viral therapies for hepatitis B and C, avoiding excessive alcohol consumption, and maintaining an active lifestyle with a balanced diet.

HCC is often asymptomatic in its early stages. At advanced stages, symptoms include abdominal pain, weight loss, and liver dysfunction. Routine screening in high-risk individuals, such as those with comorbidities, cirrhosis or chronic hepatitis B or C, is essential for early detection and appropriate disease management. The most common screening method is periodic abdominal ultrasonography (Singal AG et al. (2022)). While this is a relatively non-invasive and cost-effective method, it can be operator-dependent and less accurate in individuals with obesity or fatty liver disease. To improve diagnostic accuracy, ultrasound is often combined with the measurement of serum alpha-fetoprotein (AFP) levels (Tzartzeva K et al. (2018)). Elevated AFP levels (>20 ng/mL) are considered a biomarker for HCC. Additionally, imaging techniques such as CT scans or MRI and biopsies can be used to confirm diagnosis and to stage the cancer.

Curative treatments are available for early-stage HCC and include local ablative therapies, surgical resection, and liver transplantation (Llovet JM et al. (2021)). For patients who are either not candidates for surgery or transplantation or who are waiting for it, treatments such as transarterial chemoembolization (TACE) or systemic therapies like tyrosine kinase inhibitors (e.g., sorafenib or lenvatinib) can be used (Bruix J et al. (2011)). Immunotherapies, such as immune checkpoint inhibitors (e.g., pembrolizumab and nivolumab), are emerging as promising options for advanced HCC (El-Khoueiry AB et al. (2017)). Despite these advancements, the prognosis for HCC is less than 20% for most patients diagnosed at a late stage, compared to 70% for those diagnosed at an early stage (Calderon-Martinez E et al. (2023)), underscoring the importance of regular screening in high-risk populations.

Differential Abundance Analysis Results

This section presents the results of the differential protein abundance analysis, visualized through a volcano plot and summarized in the accompanying table for all three comparisons: 1) disease vs. healthy samples, 2) disease vs. diseases from the same class, and 3) disease vs. all other diseases.