Abstract
Background and AimsPrimary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines.MethodsA cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated in vitro from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell.ResultsAll the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (≥0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34–4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (P = 0.009) or without any (P<0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNFα was included.ConclusionBoth tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for predicting high-risk patients.
Highlights
Hepatic resection has been the mainstay of curative treatment for primary hepatocellular carcinoma (HCC) that is confined to the liver with satisfactory liver function preserved [1,2,3]
We further analyzed whether the serum concentrations of IL17 and IL10 were associated with tumor clinicopathological factors that were generally accepted as indicators of higher risk for HCC recurrence, including tumor size, tumor multinodularity, presence of microvascular invasion, lower grading of the tumor, and high serum level of alpha fetal protein (AFP)
As is consistent with the literature [1,5], our study showed that tumor size of greater than 5 cm in diameter significantly increased the risk of HCC early recurrence after curative resection
Summary
Hepatic resection has been the mainstay of curative treatment for primary hepatocellular carcinoma (HCC) that is confined to the liver with satisfactory liver function preserved [1,2,3]. Recurrence rates in HCC follow a 2-peak distribution: the early recurrence usually occurs within 2 years after resection and is most closely related to cancer metastasis spread; the late recurrence mainly results from de novo tumors as a consequence of the carcinogenic cirrhotic environment [5]. Recent molecular studies found that HCC recurrence after hepatic resection could be reasonably predicted, by the gene signatures of the tumor tissues themselves [6,7], and by that of adjacent non-tumorous liver tissues, including genes related to immune responses [7,8,9]. Primary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines
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