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).
