Department of General, Visceral and Transplantation Surgery, University Medicine of The Johannes Gutenberg University Mainz, D‑55131 Mainz, Germany.
1st Department of Internal Medicine, University Medicine of The Johannes Gutenberg University Mainz, D‑55131 Mainz, Germany.
Oncol Rep. 2019 Apr;41(4):2299-2310. doi: 10.3892/or.2019.6995. Epub 2019 Feb 1.
Hepatocellular carcinoma (HCC) is one of the most common human malignancies, the incidence of which is growing worldwide. The prognosis of HCC is very poor and it is often accompanied by a high rate of recurrence. Conventional chemotherapeutic approaches are largely inefficient. In order to develop novel effective methods for the early detection and prognosis of HCC, novel markers and therapeutic targets are urgently required. The present study focused on the effects of the expression of the tumor suppressor gene insulin‑like growth factor‑2 receptor (IGF2R) on patient survival and tumor recurrence in patients with HCC; this study paid specific attention to the influence of transarterial chemoembolization (TACE) prior to surgery. The mRNA expression levels of IGF2R were measured in primary human HCC and corresponding non‑neoplastic tumor‑surrounding tissue (TST) by reverse transcription‑polymerase chain reaction (RT‑PCR) (n=92). Subsequently, the associations between IGF2R expression and clinicopathological parameters, outcomes of HCC and TACE pretreatment prior to surgery were determined. Furthermore, the effects of the IGF2R gene polymorphisms rs629849 and rs642588 on susceptibility and on clinicopathological features of HCC were investigated. RT‑PCR demonstrated that the mRNA expression levels of IGF2R were downregulated in HCC compared with in TST samples (P=0.004), which was associated with a worse recurrence‑free survival of patients with HCC (P=0.002) and a lower occurrence of cirrhosis (P=0.05). TACE‑pretreated patients with HCC (n=26) exhibited significantly higher IGF2R mRNA expression in tumor tissues (P=0.019). In addition, significantly more patients with HCC in the TACE‑pretreated group exhibited upregulated IGF2R mRNA expression compared with in the non‑treated patients (P=0.032). The IGF2R SNPs rs629849 and rs642588 were not significantly associated with HCC risk, whereas a homozygous IGF2R rs629849 GG genotype was associated with a significantly elevated risk of non‑viral liver cirrhosis (P=0.05). In conclusion, these data suggested an important role for IGF2R expression in HCC, particularly with regards to TACE treatment prior to surgery.
肝细胞癌 (HCC) 是最常见的人类恶性肿瘤之一,其发病率在全球范围内呈上升趋势。HCC 的预后非常差,常常伴随着高复发率。传统的化疗方法在很大程度上效率低下。为了开发用于 HCC 早期检测和预后的新方法,迫切需要新的标记物和治疗靶点。本研究主要关注肿瘤抑制基因胰岛素样生长因子 2 受体 (IGF2R) 的表达对 HCC 患者生存和肿瘤复发的影响;本研究特别关注手术前经动脉化疗栓塞术 (TACE) 的影响。通过逆转录聚合酶链反应 (RT-PCR) (n=92) 测量原发性人 HCC 和相应的非肿瘤肿瘤周围组织 (TST) 中 IGF2R 的 mRNA 表达水平。随后,确定 IGF2R 表达与 HCC 临床病理参数、结局以及手术前 TACE 预处理之间的关系。此外,还研究了 IGF2R 基因多态性 rs629849 和 rs642588 对 HCC 易感性和临床病理特征的影响。RT-PCR 结果显示,与 TST 样本相比,IGF2R 的 mRNA 表达水平在 HCC 中下调 (P=0.004),这与 HCC 患者无复发生存率较差 (P=0.002) 和肝硬化发生率较低有关 (P=0.05)。接受 TACE 预处理的 HCC 患者 (n=26) 肿瘤组织中 IGF2R mRNA 表达显著升高 (P=0.019)。此外,与未接受治疗的患者相比,TACE 预处理组中 IGF2R mRNA 表达上调的 HCC 患者明显更多 (P=0.032)。IGF2R SNPs rs629849 和 rs642588 与 HCC 风险无显著相关性,而 IGF2R rs629849 GG 纯合基因型与非病毒性肝硬化的风险显著升高相关 (P=0.05)。综上所述,这些数据表明 IGF2R 表达在 HCC 中具有重要作用,特别是与手术前 TACE 治疗有关。