A new insight on the stem cell growth factor beta as astrong predictor of therapy response in hepatocellular carcinoma

Background and Aims: Inflammatory molecules such as cytokines and growth factors are important factors in the development of hepatocellular carcinoma (HCC). The stem cell growth factor beta (SCGFβ), a newly found protein, is a secreted glycoprotein functions as a growth factor for primitive hematopoietic progenitor cells. The level SCGFβ was elevated in several cancer types, but there is no information on this protein in the clinical study of HCC. The aim of this study is to investigate inflammatory biomarkers in predicting the responsiveness of therapy in HCC patients receiving radiofrequency ablation (RF) or trans-arterial chemoembolization (TACE) with focus on the SCGFβ. Method: A multiplex immunoassay panel of 48 cytokines and growth factors were used to screen 64 sera from 29 patients (age mean 72 ± 7 y.o, M22/F7, 9 HCV and 20 alcohol/metabolic) at pretreatment (T0) and 1 month (T1) after RF (n = 15) or TACE (n = 14) treatment. A quantitative real time PCR was performed to analyze gene expression of CLEC11A (SCGF) from 37 PBMC isolates. Diagnosis of HCC was established based on radiologic findings according to EASL criteria and treatment response was evaluated according to mRECIST criteria. Statistical analysis was performed by using SPSS program for non-parametric test (Whitney-Mann) and T-test. Results: At T0, different factors including cytokines IL-8 (p < 0.01), IL-15, IL-12p40, IL-17 (p < 0.05), and growth factor SCGFβ (p < 0.01) could distinguish responders to non-responders. At T0 and T1, SCGFβ could predict good response (complete response, partial response vs stable disease, and progression of disease). Its concentration was highest in non-responders, followed by early recurrence, and the lowest in complete responders, independently from HCV, BCLC stage, and type of treatment. Low SCGF level seemed to be correlated with longer disease-free survival. Analysis of PBMC isolates showed the up-regulation of CLEC11A (SCGF) mRNA expression at the T1 only in non-responders. This pattern was confirmed by using 8 paired samples. CLEC11A T1/T0 ratio was low (0.4 ± 0.2 fold) in responders, while it was almost three times higher (1.4 ± 0.8 fold) in nonresponders patients (p < 0.05).