Recipient C6 rs9200 genotype is associated with hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population

Abstract

Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired immune responses, as well as cancer immune surveillance. However, studies assessing the association between C6 and HCC recurrence after OLT are scarce. This study aimed to evaluate the association of donor and recipient C6 single-nucleotide polymorphisms with the risk for HCC recurrence after OLT. A total of 71 adult patients who underwent primary LT for HCC were enrolled. HCC recurrence was observed in 26 (36.6%) patients. Ten single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups. Patients with the rs9200 heterozygous GA variant presented significantly higher HCC recurrence rates (54.17 vs 27.66%, P=0.028), and lower cumulative tumor-free survival and overall survival (P=0.006 and P=0.013, respectively) compared with those harboring the GG/AA genotype, in multivariate logistic regression and Cox regression analyses. The rs9200 heterozygous GA variant in C6 persisted as a statistically independent prognostic factor (P<0.05) for predicting HCC recurrence after OLT. In conclusion, recipient C6 rs9200 polymorphism is associated with HCC recurrence after OLT, and improves the predictive value of clinical models.

Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFβ-Induced EMT in Ovarian Cancer

“…However, as a bridge to the clinic, lots of studies [16–19] have shown that implanting human tumor cells orthotopically into the organs of nude mice corresponding to the primary sites in humans results in an increased rate of metastasis in comparison with subcutaneous implantation and orthotopic implantation maybe provide a suitable micro-environment in which ovarian cancer have its intrinsic clinically-relevant properties [16,17,20]. Meanwhile, the orthotopic implantation models have been widely used in several studies on western drugs [21] and traditional Chinese medicines [22–26] as well as bacterial therapies [27–30]. In future studies, we will orthotopically implant human ovarian cancer tissues into nude mice and evaluate the function of CFG in these models.…”

Albumin-bilirubin grade as a prognostic factor of hepatocellular carcinoma after treatment with orthotopic liver transplantation

“…Recently, some clinical manifestations and gene mechanisms were shown to be related to post-transplantation prognosis and recurrence. Indeed, tumor size and number, histological grade of differentiation, microvascular and macrovascular invasion, ischemia time, SMO and the C6 genotype are associated with postoperative prognosis and recurrence after OLT ( 2 - 7 , 18 ). However, these factors require invasive or noninvasive assays, which are expensive and/or intolerable.…”

“…Meanwhile, orthotopic liver transplantation (OLT) still represents the best tool predicting long-term survival in the treatment of liver malignancy. Clinical prognosis and therapeutic options in HCC after OLT widely depend on both tumor recurrence and hepatic function ( 2 , 3 ). Currently, tumor size, histological grade of differentiation, microvascular and macrovascular invasion, ischemia time, and some related genes are prognostic factors after OLT in patients with HCC ( 4 - 7 ).…”

Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma

“…[12] Interestingly, we demonstrated that patients with C6 rs9200 GA presented with HCC recurrence following OLT. [13] However, to the best of our knowledge, no research has yet found the association between C6 gene polymorphisms and tacrolimus pharmacokinetics. Therefore, we initially hypothesized that C6 gene polymorphisms might regulate MAC function and mediate tacrolimus metabolism.…”