Abstract
Purpose
Renal cell carcinoma (RCC) is characterized by a variable and unpredictable clinical course. Thus, accurate prediction of the prognosis is important in clinical settings. We conducted microarray-based study to identify a novel prognostic marker in conventional RCC.
Patients and methods
The present study included the patients surgically treated at Kyoto University Hospital. Gene expression profiling of 39 samples was carried out to select candidate prognostic markers. Quantitative real-time PCR of 65 samples confirmed the microarray experiment results. Finally, we evaluated the significance of potential markers at their protein expression level by immunohistochemically analyzing 230 conventional RCC patients.
Results
Using expression profiling analysis, we identified 14 candidate genes whose expression levels predicted unfavorable disease-specific survival. Next, we examined the expression levels of nine candidate genes by quantitative real-time PCR and selected CUB-domain containing protein 1 (CDCP1) for further immunohistochemical analysis. Positive staining for CDCP1 inversely correlated with disease-specific and recurrence-free survivals. In multivariate analysis including clinical/pathological factors, CDCP1 staining was a significant predictor of disease-specific and recurrence-free survivals.
Conclusions
We identified CDCP1 as a potential prognostic marker for conventional RCC. Further studies might be required to confirm the prognostic value of CDCP1 and to understand its function in RCC progression.
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References
Bhatt AS, Erdjument-Bromage H, Tempst P, Craik CS, Moasser MM (2005) Adhesion signaling by a novel mitotic substrate of src kinases. Oncogene 24:5333–5343
Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG (2002) Understanding familial and non-familial renal cell cancer. Hum Mol Genet 11:2489–2498
Chuaqui RF, Bonner RF, Best CJ, Gillespie JW, Flaig MJ, Hewitt SM, Phillips JL, Krizman DB, Tangrea MA, Ahram M, Linehan WM, Knezevic V, Emmert-Buck MR (2002) Post-analysis follow-up and validation of microarray experiments. Nat Genet 32(Suppl):509–514
Gleave ME, Elhilali M, Fradet Y, Davis I, Venner P, Saad F, Klotz LH, Moore MJ, Paton V, Bajamonde A (1998) Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group. N Engl J Med 338:1265–1271
Goldstein NS (1999) Grading of renal cell carcinoma. Urol Clin North Am 26:637–642
Hooper JD, Zijlstra A, Aimes RT, Liang H, Claassen GF, Tarin D, Testa JE, Quigley JP (2003) Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen. Oncogene 22:1783–1794
Ihaka R, Gentlaman R (1996) R: a language for data analysis and graphics. J Comput Graph Stat 5:299–314
Ikeda JI, Morii E, Kimura H, Tomita Y, Takakuwa T, Hasegawa JI, Kim YK, Miyoshi Y, Noguchi S, Nishida T, Aozasa K (2006) Epigenetic regulation of the expression of the novel stem cell marker CDCP1 in cancer cells. J Pathol 210:75–84
Jin JS, Chen A, Hsieh DS, Yao CW, Cheng MF, Lin YF (2006) Expression of serine protease matriptase in renal cell carcinoma: correlation of tissue microarray immunohistochemical expression analysis results with clinicopathological parameters. Int J Surg Pathol 14:65–72
Jones J, Otu H, Spentzos D, Kolia S, Inan M, Beecken WD, Fellbaum C, Gu X, Joseph M, Pantuck AJ, Jonas D, Libermann TA (2005) Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res 11:5730–5739
Kim HL, Seligson D, Liu X, Janzen N, Bui MH, Yu H, Shi T, Belldegrun AS, Horvath S, Figlin RA (2005) Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma. J Urol 173:1496–1501
Kosari F, Parker AS, Kube DM, Lohse CM, Leibovich BC, Blute ML, Cheville JC, Vasmatzis G (2005) Clear cell renal cell carcinoma: gene expression analyses identify a potential signature for tumor aggressiveness. Clin Cancer Res 11:5128–5139
Lam JS, Shvarts O, Leppert JT, Figlin RA, Belldegrun AS (2005) Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. J Urol 173:1853–1862
Maruyama R, Yamana K, Itoi T, Hara N, Bilim V, Nishiyama T, Takahashi K, Tomita Y (2006) Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma. Br J Cancer 95:1244–1249
Mejean A, Oudard S, Thiounn N (2003) Prognostic factors of renal cell carcinoma. J Urol 169:821–827
Motzer RJ, Russo P (2000) Systemic therapy for renal cell carcinoma. J Urol 163:408–417
Neben K, Korshunov A, Benner A, Wrobel G, Hahn M, Kokocinski F, Golanov A, Joos S, Lichter P (2004) Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival. Cancer Res 64:3103–3111
Nentwich HA, Mustafa Z, Rugg MS, Marsden BD, Cordell MR, Mahoney DJ, Jenkins SC, Dowling B, Fries E, Milner CM, Loughlin J, Day AJ (2002) A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression. J Biol Chem 277:15354–15362
Scherl-Mostageer M, Sommergruber W, Abseher R, Hauptmann R, Ambros P, Schweifer N (2001) Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer. Oncogene 20:4402–4408
Shimazui T, Oosterwijk E, Debruyne FM, Schalken JA (1996) Molecular prognostic factor in renal cell carcinoma. Semin Urol Oncol 14:250–255
Shimazui T, Kojima T, Onozawa M, Suzuki M, Asano T, Akaza H (2006) Expression profile of N-cadherin differs from other classical cadherins as a prognostic marker in renal cell carcinoma. Oncol Rep 15:1181–1184
Stadler WM (2005) Targeted agents for the treatment of advanced renal cell carcinoma. Cancer 104:2323–2333
Sultmann H, von Heydebreck A, Huber W, Kuner R, Buness A, Vogt M, Gunawan B, Vingron M, Fuzesi L, Poustka A (2005) Gene expression in kidney cancer is associated with cytogenetic abnormalities, metastasis formation, and patient survival. Clin Cancer Res 11:646–655
Takahashi M, Rhodes DR, Furge KA, Kanayama H, Kagawa S, Haab BB, Teh BT (2001) Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification. Proc Natl Acad Sci USA 98:9754–9759
Vasselli JR, Shih JH, Iyengar SR, Maranchie J, Riss J, Worrell R, Torres-Cabala C, Tabios R, Mariotti A, Stearman R, Merino M, Walther MM, Simon R, Klausner RD, Linehan WM (2003) Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor. Proc Natl Acad Sci USA 100:6958–6963
Yeatman TJ (2004) A renaissance for SRC. Nat Rev Cancer 4:470–480
Yonezawa Y, Nagashima Y, Sato H, Virgona N, Fukumoto K, Shirai S, Hagiwara H, Seki T, Ariga T, Senba H, Suzuki K, Asano R, Hagiwara K, Yano T (2005) Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cells. Mol Carcinog 43:188–197
Acknowledgments
This work was supported in part by NEDO (New Energy and Industrial Technology Development Organization) through its “Project for Developing Biotechnology IT Integration Equipment (P03013).”
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432_2008_412_MOESM1_ESM.tif
Fig. 1S. Survival curves for patients with conventional RCC in relation to the expression of 9 candidate genes. CDCP1 expression was significantly associated with prognosis (shown in the rounded rectangle) (TIFF 55 kb)
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Awakura, Y., Nakamura, E., Takahashi, T. et al. Microarray-based identification of CUB-domain containing protein 1 as a potential prognostic marker in conventional renal cell carcinoma. J Cancer Res Clin Oncol 134, 1363–1369 (2008). https://doi.org/10.1007/s00432-008-0412-4
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DOI: https://doi.org/10.1007/s00432-008-0412-4