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Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma

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Abstract

Background

Aberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC.

Methods

We studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting.

Results/Conclusion

High ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.

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Authors and Affiliations

  1. Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan

    Masaki Kaibori, Tatsuma Sakaguchi, Morihiko Ishizaki, Kosuke Matsui, Hiroya Iida, Yoshito Tanaka, Hirokazu Miki, Richi Nakatake, Tadayoshi Okumura, Katsuji Tokuhara, Kentaro Inoue & Masanori Kon

  2. Department of Cytopathology, Kansai Medical University, Moriguchi, Japan

    Nobuaki Shikata

  3. Division of Surgery, Wada Hospital, Osaka, Japan

    Jouji Wada

  4. Division of Surgery, Wakakusa Daiich Hospital, Higashiosaka, Japan

    Michio Oda

  5. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Japan

    Mikio Nishizawa

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  1. Masaki Kaibori
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  2. Nobuaki Shikata
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Correspondence to Masaki Kaibori.

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Kaibori, M., Shikata, N., Sakaguchi, T. et al. Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma. Dig Dis Sci 60, 919–928 (2015). https://doi.org/10.1007/s10620-014-3417-7

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  • DOI: https://doi.org/10.1007/s10620-014-3417-7

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