High interleukin‑8 and/or extracellular signal‑regulated kinase 2 expression predicts poor prognosis in patients with hepatocellular carcinoma

Abstract

Interleukin (IL)-8 and extracellular signal-regulated kinase (ERK) 2 play key roles in tumor progression, but the relationship between IL-8 and/or ERK2 expression in hepatocellular carcinoma (HCC) tissues and postoperative recurrence or survival is unclear. The expression levels of IL-8 and ERK2 in both HCC tissues and non-tumor liver tissues were analyzed using the Oncomine™ database and immunohistochemistry assay. Reverse transcription-quantitative PCR was then used to evaluate the expression levels of IL-8 and ERK2 in the tumor tissues of 67 patients with HCC undergoing radical hepatectomy. Pearson's correlation, Kaplan-Meier, Cox univariate and multivariate survival analyses were utilized to determine the correlation between IL-8 and ERK2 expression in HCC tissues, and their potential prognostic significance. As indicated by the data from the Oncomine™ database, and the patient samples, IL-8 and ERK2 were expressed at significantly higher levels in HCC tissues than in non-tumor liver tissues (P<0.05). The rates of high IL-8 and ERK2 expression in HCC tissues were 43.28 (29/67) and 34.33% (23/67), respectively, and the IL-8 and ERK2 expression levels were positively correlated (r=0.764; P<0.001). Both ERK2 expression and IL-8/ERK2 co-expression were significantly associated with tumor size and differentiation (P<0.05). Additionally, high expression levels of IL-8, ERK2 and IL-8/ERK2 co-expression were all significantly associated with poor overall survival (OS; P<0.05) and disease-free survival (DFS; P<0.05). Multivariate Cox regression analysis also showed that high expression levels of IL-8, ERK2, and IL-8 and ERK2 were independent prognostic factors for OS and DFS (P<0.05). The results of the present study indicate a significant increase in the risk of recurrence and mortality in HCC patients with high expression levels of IL-8 and/or ERK2, compared with patients with low expression. Therefore, IL-8 and ERK2 may be predictors of postoperative prognosis in patients with HCC.

The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression

“…Patients with non-SVR and lower HCV viral loads after long-term IFN/RBV treatment demonstrate CXCL8 expression in HCV-related HCC progression. Other studies have indicated that high CXCL8 expression in HCC tissues was significantly associated with tumor size, differentiation, metastasis, poor overall survival, disease-free survival, and an increased risk of recurrence and mortality [35,36]. Patients with low CXCL8 demonstrated less intrahepatic invasion and distant metastasis, lower recurrence rates, and increased overall survival time.…”

UDCA Inhibits Hypoxic Hepatocellular Carcinoma Cell–Induced Angiogenesis Through Suppressing HIF-1α/VEGF/IL-8 Intercellular Signaling

“…IL-8 could also modify the HCC microenvironment by recruiting cancer-associated neutrophils that contribute to angiogenesis ( Fousek et al, 2021 ). Several studies have demonstrated that a higher IL-8 level is associated with worse prognosis in HCC ( Deng et al, 2019 ; Shakiba et al, 2019 ). IL-8 triggered the activation of AKT and ERK in endothelial cells, which is involved in angiogenesis ( Heidemann et al, 2003 ).…”

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection

“…Furthermore, IL-8 conveys direct proangiogenic, chemotactic effects on endothelial cells via its receptors CXCR1 and -2 [ 51 ]. Most studies on IL-8 in HCC focus on the prognostic role of IL-8 expression and on the inhibition or activation of IL-8 in HCC models and cell lines [ 22 , 23 , 38 , 54 , 55 ]. As such, the findings of different groups have linked increased serum levels of IL-8 with tumor invasion, recurrence, and metastases [ 22 , 55 ].…”

“…Most studies on IL-8 in HCC focus on the prognostic role of IL-8 expression and on the inhibition or activation of IL-8 in HCC models and cell lines [ 22 , 23 , 38 , 54 , 55 ]. As such, the findings of different groups have linked increased serum levels of IL-8 with tumor invasion, recurrence, and metastases [ 22 , 55 ]. Only scarce evidence is available on the prognostic role of IL-8 germline SNPs in HCC patients undergoing curative-intent surgery [ 56 , 57 , 58 ].…”