High TNF-α And/or P38MAPK Expression Predicts a Favourable Prognosis in Patients with TNM Hepatocellular Carcinoma: An Immunohistochemical Study

Tumour necrosis factor α (TNF-α) and p38 mitogen-activated protein kinase (p38MAPK) serve an important role in regulating tumour cell apoptosis. However, a limited number of studies have investigated the predictive value of both TNF-α and p38MAPK in hepatocellular carcinoma (HCC). An integrated bioinformatics analysis was initially performed using two datasets available from the Oncomine™ database to determine the association between TNF-α and/or p38MAPK expression and prognosis of patients with HCC. Subsequently, TNF-α and p38MAPK expression in tissue samples from 83 patients with HCC classified as TNM, using the Tumour-Node-Metastasis (TNM) staging system, was investigated using immunohistochemistry. The associations between clinicopathological characteristics and different TNF-α and p38MAPK expression levels in HCC were investigated using the χ2 test. Kaplan-Meier and Cox univariate/multivariate survival analyses were performed to explore the predictive significance of TNF-α and/or p38MAPK expression in patients with HCC. Using the Oncomine™ database, it was revealed that TNF-α and/or p38MAPK expression was not significantly associated with overall survival (OS) or disease-free survival (DFS) rates; however, TNF-α and p38MAPK expression levels were positively associated (P<0.05), and high p38MAPK expression was significantly associated with low aspartate aminotransferase levels (P<0.05). Compared with low expression levels of TNF-α and p38MAPK together, high expression of TNF-α alone, p38MAPK alone and TNF-α and p38MAPK together were significantly associated with improved OS and DFS rates (P<0.05). Additionally, multivariate Cox regression models suggested that high expression levels of TNF-α alone, p38MAPK alone, or TNF-α and p38MAPK together in the HCC microenvironment were independent predictive factors for OS and DFS rates (P<0.05). Patients with TNM HCC with high TNF-α and/or p38MAPK expression had a significantly lower risk of recurrence and mortality compared with patients with low TNF-α and p38MAPK expression. Consequently, TNF-α and p38MAPK could serve as predictive biomarkers or potential therapeutic targets for TNM HCC treatment.