Expression and prognostic significance of insulin‑like growth factor-2 receptor in human hepatocellular carcinoma and the influence of transarterial chemoembolization

Lautem,Anja; Simon,Frank; Hoppe‑Lotichius,Maria; Mittler,Jens; Vollmar,Johanna; Schad,Arno; Düber,Christoph; Galle,Peter Robert; Otto,Gerd; Zimmermann,Tim; Lang,Hauke

doi:10.3892/or.2019.6995

Expression and prognostic significance of insulin‑like growth factor-2 receptor in human hepatocellular carcinoma and the influence of transarterial chemoembolization

Authors:
- Anja Lautem
- Frank Simon
- Maria Hoppe‑Lotichius
- Jens Mittler
- Johanna Vollmar
- Arno Schad
- Christoph Düber
- Peter Robert Galle
- Gerd Otto
- Tim Zimmermann
- Hauke Lang
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Affiliations: 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, Institute of Pathology, University Medicine of The Johannes Gutenberg University Mainz, D‑55131 Mainz, Germany, Department of Diagnostic and Interventional Radiology, University Medicine of The Johannes Gutenberg University Mainz, D‑55131 Mainz, Germany
Published online on: February 1, 2019 https://doi.org/10.3892/or.2019.6995
Pages: 2299-2310

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Abstract

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.

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