Tumor SOCS3 methylation status predicts the treatment response to TACE and prognosis in HCC patients

Abstract

BackgroundSuppressor of cytokine signaling (SOCS) 1 and 3 methylation have been associated with clinical features and outcomes of cancer patients. However, their roles in determining the treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) remain unknown.ResultsWe found that presence of SOCS3 methylation is significantly associated with the major clinical features of HCC patients, including tumor stage, lymph node and vascular invasion. Of note, we observed that the presence of SOCS3 methylation is closely related to TACE response. In prognosis analyses, HCC patients with SOCS3 methylation presence have a poorer prognosis indicated by lower 3-, and 5-year survival rates and shorter mean survival period, than those without. Multivariate COX analysis confirms the prognostic role of the presence of SOCS3 methylation in HCC patients receiving TACE treatment.Materials and MethodsA total of 246 HCC patients receiving TACE were enrolled in this study. Tumor samples was obtained from echo-guided fine needle aspiration and genomic DNA from tumor samples was purified. SOCS1 and SOCS3 methylation status were detected using methylation-specific polymerase chain reaction. The treatment responses to TACE of patients were evaluated after procedure and all patients were followed for prognosis analysis.ConclusionsThis finding suggests that the presence of SOCS3 methylation is a marker to predict treatment response and prognosis in HCC patients receiving TACE therapy.

COX-2/PGE2 Axis Regulates HIF2α Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment

“…Hepatocellular carcinoma (HCC) is the most common primary liver cancer (1,2). Many HCC patients lose the opportunity for surgical resection due to late diagnosis (3). Unfortunately, HCC is extremely resistant to chemotherapeutic drugs (4).…”

Phosphorylated STAT3 expression linked to SOCS3 methylation is associated with proliferative ability of gastric mucosa in patients with early gastric cancer

“…SOCS3 methylation frequently occurs in various epithelial and non-epithelial malignancies, including head and neck squamous cell carcinoma, pancreatic cancer, hepatocellular carcinoma, multiple myeloma and glioma (27)(28)(29)(30)(31). SOCS3 methylation is also detectable in various inflammation-associated gastroenterological malignancies, including hepatocellular carcinoma (39), Barrett's adenocarcinoma (40) and ulcerative colitis-associated types of colorectal cancer (41), suggesting the involvement of SOCS3 methylation in different types of inflammatory gastric cancer.…”

“…On the other hand, the suppressor of cytokine signaling 3 (SOCS3) can bind to cytokine receptors and JAK to inhibit JAK/STAT3 signaling, acting as a tumor suppressor in a negative feedback loop (25,26). In this regard, alteration of SOCS3 appears to be a crucial step of carcinogenesis in various organs, including the head and neck, pancreas, liver, blood and brain (27)(28)(29)(30)(31). The present study investigated SOCS3 methylation and p-STAT3 expression levels in the non-NGM of patients with early GC in relation to non-NGM cell proliferative ability that may impact GC development.…”

What is the best combination treatment with transarterial chemoembolization of unresectable hepatocellular carcinoma? a systematic review and network meta-analysis

“…TACE is a standard minimally invasive procedure developed for HCC patients who are not eligible for complete resection [ 4 ]. TACE involves the injection of a chemotherapeutic agent, which induces selective vascular embolization and blocks the arteries, hence triggering tumor infarction and necrosis [ 5 – 6 ] and the combination of fluorouracil, cisplatin , mitomycin or epirubicin in the TACE treatment was the most common regimen [ 7 ].Patients with large and multiple lesions exceeding the Milan criteria have been widely treated by TACE, which has been proven to improve the survival of those patients [ 8 – 10 ]. However, TACE may further affect liver functions and damage the hepatic arterial system.…”