Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma

  • Authors:
    • Kiyohiko Hotta
    • Masayuki Sho
    • Kiyohide Fujimoto
    • Keiji Shimada
    • Ichiro Yamato
    • Satoshi Anai
    • Hiroshi Harada
    • Kazutake Tsujikawa
    • Noboru Konishi
    • Nobuo Shinohara
    • Yoshiyuki Nakajima
  • View Affiliations

  • Published online on: May 29, 2015     https://doi.org/10.3892/or.2015.4017
  • Pages: 648-654
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Abstract

Prostate cancer antigen-1 (PCA-1)/ALKBH3 has been recently identified in human prostate cancer and its expression is correlated with disease progression and prognosis. However, the precise role and function of PCA-1/ALKBH3 in human malignancies are largely unknown. In the present study, we investigated the clinical significance and therapeutic potential of PCA-1/ALKBH3 in renal cell carcinoma (RCC). PCA-1/ALKBH3 expression was examined by immunohistochemistry in 101 RCC patients who underwent radical or partial nephrectomy. Its expression was positively correlated with advanced pathological T- and M-factors and TNM stage (T, P<0.05; M, P<0.01; TNM, P<0.01, respectively). In the prognostic analysis, PCA-1/ALKBH3-negative patients with RCC had a significantly better prognosis than PCA-1/ALKBH3-positive patients (5-year survival rate, 92.9 vs. 75.9%, respectively; P<0.05). Next, the therapeutic potential of targeting PCA-1/ALKBH3 was further evaluated by small interfering RNA method using a human RCC cell line (CAKI‑1). We found that PCA-1/ALKBH3 knockdown significantly inhibited the growth of CAKI-1 cells compared with the control (P<0.001). Furthermore, knockdown of PCA-1 induced apoptosis in CAKI-1 cells, as assessed by poly(ADP-ribose) polymerase‑cleavage assays. We demonstrated for the first time that PCA-1/ALKBH3 expression has a significant prognostic impact on patient prognosis in RCC. Furthermore, its knockdown has a therapeutic efficacy on RCC. Taken together, both our clinical and experimental data strongly suggest that PCA-1/ALKBH3 may be functionally important and a novel molecular target for human RCC.
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August-2015
Volume 34 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hotta K, Sho M, Fujimoto K, Shimada K, Yamato I, Anai S, Harada H, Tsujikawa K, Konishi N, Shinohara N, Shinohara N, et al: Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma. Oncol Rep 34: 648-654, 2015
APA
Hotta, K., Sho, M., Fujimoto, K., Shimada, K., Yamato, I., Anai, S. ... Nakajima, Y. (2015). Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma. Oncology Reports, 34, 648-654. https://doi.org/10.3892/or.2015.4017
MLA
Hotta, K., Sho, M., Fujimoto, K., Shimada, K., Yamato, I., Anai, S., Harada, H., Tsujikawa, K., Konishi, N., Shinohara, N., Nakajima, Y."Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma". Oncology Reports 34.2 (2015): 648-654.
Chicago
Hotta, K., Sho, M., Fujimoto, K., Shimada, K., Yamato, I., Anai, S., Harada, H., Tsujikawa, K., Konishi, N., Shinohara, N., Nakajima, Y."Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma". Oncology Reports 34, no. 2 (2015): 648-654. https://doi.org/10.3892/or.2015.4017