Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma

Miyahara, Koji; Nouso, Kazuhiro; Tomoda, Takeshi; Kobayashi, Sayo; Hagihara, Hiroaki; Kuwaki, Kenji; Toshimori, Junichi; Onishi, Hideki; Ikeda, Fusao; Miyake, Yasuhiro; Nakamura, Shinichiro; Shiraha, Hidenori; Takaki, Akinobu; Yamamoto, Kazuhide

doi:10.1111/j.1440-1746.2011.06887.x

Cited by 82 publications

(76 citation statements)

References 36 publications

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“…Low HGF levels and high c-kit levels in plasma at baseline were reported to be associated with longer survival in HCC patients treated with sorafenib (9). Several serum angiogenesis-related cytokines levels were correlated with response to sorafenib treatment (9,34). Some tissue markers, such as ␣␤-crystallin (35), FGF3/FGF4 (36), JNK (37), and pERK (38) have been reported to predict sorafenib response.…”

Section: Discussionmentioning

confidence: 99%

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Yeh¹,

Hsu

Shao

et al. 2015

Molecular & Cellular Proteomics

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Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7 R ) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7 R tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7 R cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1␣ signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Yeh¹,

Hsu

Shao

et al. 2015

Molecular & Cellular Proteomics

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“…Preoperative presence of Ang2 in the hepatic vein was also associated with portal invasion and poor outcome in HCC resected patients [111] . In a small uncontrolled cohort of patients treated with sorafenib for advanced HCC, the authors reported that Ang2 could predict the outcome [112] . High Ang2 serum baseline level was associated with PFS but not with OS in HCC patients treated with sorafenib [112] .…”

Section: Hepatocyte Growth Factormentioning

confidence: 99%

“…In a small uncontrolled cohort of patients treated with sorafenib for advanced HCC, the authors reported that Ang2 could predict the outcome [112] . High Ang2 serum baseline level was associated with PFS but not with OS in HCC patients treated with sorafenib [112] . Llovet et al [63] confirmed the negative impact on prognosis of baseline high plasma level of Ang2 in HCC.…”

Section: Hepatocyte Growth Factormentioning

confidence: 99%

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

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Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

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“…Miyahara et al measured changes in the levels of several serum angiogenesis markers before and after sorafenib treatment and showed that the number of HCC patients with progressive disease was high among HCC patients with high levels of serum angiogenesis markers before the treatment [20]. In addition, Tsuchiya et al reported that chronological changes in serum VEGF levels can serve as a useful prognostic indicator []19].…”

Section: Cytokine Biomarkersmentioning

confidence: 99%

Biomarkers and Personalized Sorafenib Therapy

Kudo¹

2014

Liver Cancer

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Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma

Abstract: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

Cited by 82 publications

References 36 publications

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Biomarkers and Personalized Sorafenib Therapy

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