Inter-alpha inhibitor h4 as a potential biomarker predicting the treatment outcomes in patients with hepatocellular carcinoma

Eun Jung Lee, Seung Hyun Yang, Kyoung Jin Kim, Hyejung Cha, Seo Jin Lee, Ji Hye Kim, Junkyu Song, Kyung Hee Chun, Jinsil Seong

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Purpose Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liverdirected therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins. Materials and Methods 2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells. Results Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis. Conclusion Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.

Original languageEnglish
Pages (from-to)646-657
Number of pages12
JournalCancer Research and Treatment
Issue number3
Publication statusPublished - 2018 Jul 1

Bibliographical note

Funding Information:
This work was supported by the Mid-career Researcher Program (NRF-2014R1A2A1A11054463) through the National Research Foundation of Korea funded by the Ministry of Science.

Publisher Copyright:
©2018 by the Korean Cancer Association.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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