Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma.
- Author:
Eun Jung LEE
1
;
Seung Hyun YANG
;
Kyoung Jin KIM
;
Hyejung CHA
;
Seo Jin LEE
;
Ji Hye KIM
;
Junkyu SONG
;
Kyung Hee CHUN
;
Jinsil SEONG
Author Information
- Publication Type:Original Article
- Keywords: Prognosis; Hepatocellular carcinoma; Liver-directed therapy; ITIH4; Biomarkers
- MeSH: Biomarkers; Carbonic Anhydrase I; Carboxyhemoglobin; Carcinoma, Hepatocellular*; Electrophoresis; Enzyme-Linked Immunosorbent Assay; Fibrinogen; Humans; Mass Spectrometry; Neoplasm Metastasis; Prognosis; Radiotherapy; Treatment Outcome
- From:Cancer Research and Treatment 2018;50(3):646-657
- CountryRepublic of Korea
- Language:English
- Abstract: 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 liver-directed 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 matrix-assisted 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.
