Association between insulin-like growth factor-2 and metastases after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma: A prospective study

BACKGROUND. Hypoxia up-regulates insulin-like growth factor-2 (IGF-2) and thus stimulates the growth of hepatocellular carcinoma (HCC) cells. In the current study, the authors prospectively evaluated changes in plasma IGF-2 levels in HCC patients after transcatheter arterial chemoembolization (TACE), which usually results in hypoxic insult to liver tissue. The authors also examined the association between changes in plasma IGF-2 levels after TACE and HCC progression, especially in relation to metastasis. METHODS. Plasma IGF-2 levels were measured before and 4 weeks after TACE in 46 patients with HCC. Three months after TACE, the patients were evaluated for the occurrence of metastatic HCC. RESULTS. In 13 of the 46 patients, post-TACE plasma IGF-2 levels decreased by > 20% (Group 1) compared with their basal levels; in 18 patients, the IGF-2 levels changed within 20% (Group 2) and in 15 patients the IGF-2 levels increased by > 20% (Group 3). Plasma IGF-2 levels had a tendency to increase in patients with large-sized tumors, high serum α-fetoprotein (AFP) levels, and the heterogeneous uptake of iodized oil. Metastatic foci were found in 9 patients in Group 3 (60%), in contrast to only 3 patients in Group 2 (17%) and in none of the patients in Group 1 (P = 0.001). On multivariate analysis, higher Child-Pugh scores and increased plasma IGF-2 levels (Group 3) were found to be independent risk factors for metastasis. CONCLUSIONS. Increased plasma IGF-2 levels after TACE, which are common in patients with large-sized tumors and high serum AFP levels, appear to be associated with the occurrence of metastatic HCC after TACE.