Serum Insulin-like Growth Factor-I Level Is an Independent Predictor of Recurrence and Survival in Early Hepatocellular Carcinoma: A Prospective Cohort Study

Abstract

Purpose: Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment.Experimental Design: Consecutive patients with hepatocellular carcinoma who had undergone surgical resection, radiofrequency ablation, or percutaneous ethanol injection as curative treatments of early hepatocellular carcinoma were included from two prospective cohorts and the training set (n ¼ 101) and the validation set (n ¼ 91) were established. Serum samples were collected before treatment and the levels of IGF-I and IGF-binding protein-3 (IGFBP-3) were analyzed with regard to their associations with recurrence and survival.Results: In the training set, patients with low IGF-I levels showed significantly shorter TTR [median, 14.6 months; 95% confidence interval (CI), 1.8-27.5] than patients with high IGF-I levels (median, 50.8 months; 95% CI, 36.9-64.7; P < 0.001) during a median follow-up period of 52.4 months. In the multivariate analysis, low levels of IGF-I were an independent predictor of recurrence (HR, 2.49; 95% CI, 1.52-4.08; P < 0.001). Furthermore, together with high-serum a-fetoprotein and multiple tumors, low levels of IGF-I remained an independent predictor of poorer survival (HR, 8.00; 95% CI, 1.94-33.01; P ¼ 0.004). Applied to the independent validation set, low-serum IGF-I levels maintained their prognostic value for shorter TTR and OS.Conclusions: Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment. Clin Cancer Res; 19(15); 4218-27. Ó2013 AACR.

HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia

“…The liver, which is crucial in whole-body metabolic homeostasis, has been shown to participate in causing skeletal muscle wasting when compromised (Anand, 2017;Bhanji et al, 2017;De Bandt et al, 2018). Two hepatokines known to play a role in skeletal muscle homeostasis and pathogenesis of multiple diseases, including cancer cachexia, are the anabolic factor IGF1 and the catabolic factor IL6 (Song et al, 2013;Attard-Montalto et al, 1998;Bonetto et al, 2013;Costelli et al, 2006;Cho et al, 2013;Huber et al, 2018). The data presented in the current study support the notion that formation of LM, as occurring in CRC, may further perturb the hepatic production of IGF1 and IL6, thus exacerbating the potential for muscle wasting (Norris et al, 2014;Bonetto et al, 2012Bonetto et al, , 2011Ueda et al, 1994;Baltgalvis et al, 2009;White et al, 2013).…”

Validation of a Modified Child-Turcotte-Pugh Classification System Utilizing Insulin-Like Growth Factor-1 for Patients with Hepatocellular Carcinoma in an HBV Endemic Area

“…[30–33] Furthermore, other studies suggested that lower plasma levels of IGF-1 were strongly associated with more advanced HCC parameters. [34–36] Since HCC cells suppress normal hepatic function by replacing normal hepatocytes, advanced HCC might reduce IGF-1 synthesis to a greater extent than early HCC. In fact, our study showed that lower levels of serum IGF-1 were significantly related to more advanced AJCC stages.…”

Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma

“…The insulin-like growth factor (IGF) signaling pathway is associated with HCC cell growth and is important during the development and progression of HCC (5). IGF-I, IGF-II and their corresponding receptors mediate the biological functions of the IGF signaling pathway through the activation of the mitogen-activated protein kinase signaling pathway, which is involved in cell growth and metabolism (6,7).…”