Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma

Hirotaka Shoji, Sachiyo Yoshio, Yohei Mano, Hiroyoshi Doi, Masaya Sugiyama, Yosuke Osawa, Kiminori Kimura, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Yoshihiko Aoki, Moto Fukai, Akinobu Taketomi, Masashi Mizokami, Tatsuya Kanto

Research output: Contribution to journalArticle

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Abstract

Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis. We analyzed 25 advanced HCC patients and prospectively evaluated TEMs before (Pre TEMs) and at 1 month after initial therapy (T1m TEMs). The radiologic response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Median survival time (MST) was significantly longer in the partial response/stable disease (PR/SD) group (21.8 months) than in the PD group (8.7 months). ΔTEMs (changes of T1m TEMs compared to Pre TEMs) were significantly lower in the PR/SD group than in the PD group. MST of the ΔTEMs low group (14.2 months) was significantly longer than that of the high group (8.7 months). Univariate and multivariate Cox regression analyses showed that ΔTEMs [hazard ratio (HR) = 8.53, 95% confidence interval (CI) = 1.51–48.16, p = 0.015] and Child-Pugh class (HR = 5.59, 95% CI = 1.06–29.63, p = 0.043) were independently associated with overall survival. Our results suggest that ΔTEMs could serve as a biomarker for predicting radiologic response and overall survival in sorafenib-treated patients with advanced HCC.

Original languageEnglish
Pages (from-to)1011-1017
Number of pages7
JournalInternational Journal of Cancer
Volume141
Issue number5
DOIs
Publication statusPublished - Sep 1 2017

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Monocytes
Hepatocellular Carcinoma
Biomarkers
Survival
Confidence Intervals
sorafenib
Phosphotransferases
Regression Analysis
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma. / Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Doi, Hiroyoshi; Sugiyama, Masaya; Osawa, Yosuke; Kimura, Kiminori; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aoki, Yoshihiko; Fukai, Moto; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya.

In: International Journal of Cancer, Vol. 141, No. 5, 01.09.2017, p. 1011-1017.

Research output: Contribution to journalArticle

Shoji, H, Yoshio, S, Mano, Y, Doi, H, Sugiyama, M, Osawa, Y, Kimura, K, Arai, T, Itokawa, N, Atsukawa, M, Aoki, Y, Fukai, M, Taketomi, A, Mizokami, M & Kanto, T 2017, 'Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma', International Journal of Cancer, vol. 141, no. 5, pp. 1011-1017. https://doi.org/10.1002/ijc.30804
Shoji, Hirotaka ; Yoshio, Sachiyo ; Mano, Yohei ; Doi, Hiroyoshi ; Sugiyama, Masaya ; Osawa, Yosuke ; Kimura, Kiminori ; Arai, Taeang ; Itokawa, Norio ; Atsukawa, Masanori ; Aoki, Yoshihiko ; Fukai, Moto ; Taketomi, Akinobu ; Mizokami, Masashi ; Kanto, Tatsuya. / Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma. In: International Journal of Cancer. 2017 ; Vol. 141, No. 5. pp. 1011-1017.
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AU - Shoji, Hirotaka

AU - Yoshio, Sachiyo

AU - Mano, Yohei

AU - Doi, Hiroyoshi

AU - Sugiyama, Masaya

AU - Osawa, Yosuke

AU - Kimura, Kiminori

AU - Arai, Taeang

AU - Itokawa, Norio

AU - Atsukawa, Masanori

AU - Aoki, Yoshihiko

AU - Fukai, Moto

AU - Taketomi, Akinobu

AU - Mizokami, Masashi

AU - Kanto, Tatsuya

PY - 2017/9/1

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N2 - Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis. We analyzed 25 advanced HCC patients and prospectively evaluated TEMs before (Pre TEMs) and at 1 month after initial therapy (T1m TEMs). The radiologic response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Median survival time (MST) was significantly longer in the partial response/stable disease (PR/SD) group (21.8 months) than in the PD group (8.7 months). ΔTEMs (changes of T1m TEMs compared to Pre TEMs) were significantly lower in the PR/SD group than in the PD group. MST of the ΔTEMs low group (14.2 months) was significantly longer than that of the high group (8.7 months). Univariate and multivariate Cox regression analyses showed that ΔTEMs [hazard ratio (HR) = 8.53, 95% confidence interval (CI) = 1.51–48.16, p = 0.015] and Child-Pugh class (HR = 5.59, 95% CI = 1.06–29.63, p = 0.043) were independently associated with overall survival. Our results suggest that ΔTEMs could serve as a biomarker for predicting radiologic response and overall survival in sorafenib-treated patients with advanced HCC.

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