title: Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma.
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.
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.affiliation: Department of Urology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Pathology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamato
authors.affiliation: Department of Urology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Anai
authors.affiliation: Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
authors.affiliation: Department of Pathology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.affiliation: Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C505096:PCA-1 antigen, human