Serum Soluble TWEAK Concentration is Decreased in Patients with Hepatocellular Cancer and Low Blood Levels of sTWEAK are Associated with Poor Survival.

Abstract

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily and has been implicated in the pathogenesis of several cancers. This study was conducted to investigate serum sTWEAK levels and its relation with prognosis in patients with hepatocellular carcinoma (HCC). Twenty-eight cirrhotic patients with HCC, 28 patients with cirrhosis and 30 healthy subjects were included in the study. Serum sTWEAK concentrations were measured by using commercially available enzyme-linked immune sorbent assay kits. Mean serum sTWEAK concentrations in HCC, cirrhosis and healthy control groups were 174.0±69.9 pg/ml, 221.4±61.2 pg/ml and 288.0±68.4 pg/ml respectively and the difference between the groups was statistically significant (p< 0.001). Mean sTWEAK concentration in the HCC group was significantly lower than both cirrhosis group (p= 0.009) and healty controls (p< 0.001). In the ROC curve analysis, AUC for serum TWEAK concentration to predict one-year mortality in HCC patients was 0.836 (95% CI: 0.684-0.987) and for the specified cut-off value of 148.1 pg/ml, sensitivity and specificity were 66.7% and 92.3% respectively. Kaplan-Meier survival estimates showed that, survival rate was significantly lower in patients with serum sTWEAK< 148.1 pg/ml (log-rank test, chi-square= 11.75, p= 0.001). Serum sTWEAK concentration was identified as an independent predictor of mortality in Cox regression analysis (Hazard ratio= 4.325, %95 CI: 1.080-17.326, p= 0.025). Serum sTWEAK concentration is decreased in HCC patients. Lower serum sTWEAK concentrations at the time of diagnosis are associated with poor prognosis and higher one-year mortality rates in HCC patients.Keywords: Tumor necrosis factor-like weak inducer of apoptosis, Hepatocellular cancer, Survival rate, Mortality ÖZET Serum Solubl TWEAK Konsantrasyonu Hepatoselüler Kanser Hastalarında Azalmıştır ve Düşük Kan sTWEAK Düzeyleri Kötü Sağkalımla İlişkilidirTumor necrosis factor-like weak inducer of apoptosis (TWEAK) tümör nekrozis factor ailesinin bir üyesidir ve birçok kanserin patogenezinde rol oynadığı öne sürülmüştür. Bu çalışmada hepatoselüler kanser (HCC) hastalarında serum sTWEAK düzeylerinin araştırılması amaçlanmıştır. Yirmi sekiz HCC hastası, 28 siroz hastası ve 30 sağlıklı kontrol çalışmaya dahil edilerek serum sTWEAK konsantrasyonları ELISA yöntemiyle hazır kitler kullanılarak çalışılmıştır. HCC, siroz ve sağlıklı kontrol gruplarında ortalama serum sTWEAK konsantrasyonları 174.0±69.9 pg/ml, 221.4±61.2 pg/ml ve 288.0±68.4 pg/ml olup gruplar arasındaki fark istatistiksel olarak anlamlıydı (p< 0.001). HCC grubundaki ortalama sTWEAK konsantrasyonunun gerek siroz (p= 0.009) gerek de sağlıklı kontrol (p< 0.001) gruplarından daha düşük olduğu görüldü. ROC analizinde, sTWEAK için 1 yıllık mortaliteyi öngörme açısından eğri altında kalan alan 0.836 (%95CI: 0,684-0,987) ve belirlenen148,1 pg/ml eşik değeri için duyarlılık ve özgüllük %66.7 ve %92.3 olarak bulundu.Kaplan-Meier sağkalım analizi ile serum sTWEAK konsantrasyon...