Open Access

Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma

  • Authors:
    • Tomoki Kohno
    • Asahiro Morishita
    • Hisakazu Iwama
    • Koji Fujita
    • Joji Tani
    • Kei Takuma
    • Mai Nakahara
    • Kyoko Oura
    • Tomoko Tadokoro
    • Takako Nomura
    • Hirohito Yoneyama
    • Kiyohito Kato
    • Keiichi Okano
    • Yasuyuki Suzuki
    • Akira Nishiyama
    • Takashi Himoto
    • Tsutomu Masaki
  • View Affiliations

  • Published online on: June 5, 2020     https://doi.org/10.3892/ol.2020.11696
  • Pages: 1727-1733
  • Copyright: © Kohno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‑related death worldwide. Clinical management has improved the prognosis of early HCC, but that of advanced HCC remains poor. Sorafenib, an oral multikinase inhibitor, provided a treatment option for advanced‑stage HCC, and prolonged the survival and inhibited tumor progression as first‑line therapy in patients with advanced HCC. In this study, we investigated if specific microRNAs could act as predictive biomarkers of sorafenib effectiveness and indicate the best time to switch to second‑line therapies. Sorafenib inhibited the proliferation of the Li‑7, Hep3B, HepG2 and Huh7 liver cancer cell lines (effective group), but not that of the HLE, HLF and ALEX cancer cell lines (non‑effective group). A microRNA (miRNA/miR) analysis was performed comparing sorafenib‑effective and non‑effective cells lines as well as serum samples from patients with HCC from sorafenib‑effective (complete response/partial response) and ‑non‑effective (progressive disease) groups before sorafenib administration and detected three differentially‑expressed miRNAs that were common among the in vivo and in vitro samples. The increase rate (effective/non‑effective) of hsa‑miR‑30d in the medium was higher than that in the cancer cells. hsa‑miR‑30d was highly expressed in the serum and exosomes of patients with HCC in the effective group when compared to those of the non‑effective group. Additionally, the hsa‑miR‑30d expression in the medium of cancer cell lines was highly upregulated in the effective group compared with the non‑effective group. These results suggested that hsa‑miR‑30d might be secreted by the cancer cells to the serum through the exosomes. We identified a specific circulating miRNA that is related to refractory HCC under sorafenib therapy. Therefore, hsa‑miR‑30d might serve as a predictive biomarker for the efficacy of sorafenib therapy in HCC.

Related Articles

Journal Cover

August-2020
Volume 20 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Kohno, T., Morishita, A., Iwama, H., Fujita, K., Tani, J., Takuma, K. ... Masaki, T. (2020). Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma. Oncology Letters, 20, 1727-1733. https://doi.org/10.3892/ol.2020.11696
MLA
Kohno, T., Morishita, A., Iwama, H., Fujita, K., Tani, J., Takuma, K., Nakahara, M., Oura, K., Tadokoro, T., Nomura, T., Yoneyama, H., Kato, K., Okano, K., Suzuki, Y., Nishiyama, A., Himoto, T., Masaki, T."Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma". Oncology Letters 20.2 (2020): 1727-1733.
Chicago
Kohno, T., Morishita, A., Iwama, H., Fujita, K., Tani, J., Takuma, K., Nakahara, M., Oura, K., Tadokoro, T., Nomura, T., Yoneyama, H., Kato, K., Okano, K., Suzuki, Y., Nishiyama, A., Himoto, T., Masaki, T."Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma". Oncology Letters 20, no. 2 (2020): 1727-1733. https://doi.org/10.3892/ol.2020.11696