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Serum proteomic pattern for predicting recurrence of undifferentiated nasopharyngeal carcinoma after radiotherapy
A potential surrogate marker
Clinical Proteomics volume 1, pages 365–373 (2004)
Abstract
Although most patients with early-stage nasopharyngeal carcinoma (NPC) can be cured by radiotherapy, there is a high recurrence rate in patients with advanced NPC. We attempted to identify proteomic patterns in sera for predicting tumor recurrence. Pretreatment sera were collected from 64 NPC patients with complete remission after radiotherapy. Serum proteins were profiled by SELDI ProteinChip technology, and correlated with local/distant recurrence.
Forty proteomic features were significantly different between the patient groups with and without tumor recurrence. Univariate analyses showed that 32 of them were significantly associated with time to first recurrence. Multivariate Cox-regression analyses identified International Union Against Cancer (UICC) stage and two proteomic features with mass/charge (m/z) values of 8808 and 6626 as independent prognostic indicators for tumor recurrence. The hazard ratios were 2.0 (95% confidence interval, CI 1.3–3.2) and 0.79 (95% CI 0.64–0.96) for a double of peak intensity of proteomic feature m/z 8808 and m/z 6626, respectively. These two proteomic features were also independent prognosticators for overall survival. A decision tree was constructed to predict the tumor recurrence by using UICC stage, proteomic feature m/z 8808, and proteomic feature m/z 6626, and evaluated by Leave-One-Out crossvalidation. Kaplan-Meier analysis confirmed that the decision tree could predict both recurrencefree survival and overall survival. The positive and negative predictive values for tumor recurrence within 4 yr were 74 and 89%, respectively.
A serum proteomic pattern comprising features m/z 8808 and m/z 6626 is a potential surrogate marker of disease recurrence after radiotherapy in NPC.
References
Ho, J.H.C. (1978) An epidemiologic and clinical study of nasopharyngeal carcinoma. Int. J. Radiat. Oncol. Bio. Phys. 4:183–205.
Teo, P.M., Yu, P., Lee, W.Y., Leung, S.F., Kwan, W.H., Yu, K.H., et al. (1996) Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography. Int. J. Radiat. Oncol. Biol. Phys. 36:291–304.
Petricoin III, E.F., Ardekani, A.M., Hitt, A.B., Levine, P.J., Fusaro, V.A., Steinberg, S.M., et al. (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359:572–577.
Poon, T.C.W., Yip, T.T., Chan, A.T.C., Yip, C., Yip, V., Mok, T.S.K., et al. (2003) Comprehensive proteomic profiling identifies serum preteomic signatures for detection of hepatocellular carcinoma and its subtypes. Clin. Chem. 49:752–760.
Poon, T.C.W., Chan, K.C.A., Ng, P.C., Chiu, R.W.K., Ang, I.L., Tong, Y.K., et al. (2004) Serial analysis of plasma proteomic signatures in pediatric patients with severe acute respiratory syndrome and correlation with viral load. Clin. Chem. 50:1452–1455.
Poon, T.C.W., Hui, A.Y., Chan, H.L.Y., Ang, I.L., Chow, S.M., Wong, N., et al. (2005) Prediction of liver fibrosis and cirrhosis in chronic Hepatitis B Infection by serum proteomic Fingerprinting: a pilot study. Clin Chem. in press.
Cho, W.C., Yipm, T.T., Yip, C., Yip, V., Thulasiraman, V., Ngan, R.K.C., et al. (2004) Identification of serum amyloid a protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling. Clin. Cancer Res. 10:43–52.
Xiao, Z., Luke, B.T., Izmirlian, G., Umar, A., Lynch, P.M., Phillips, R.K., et al. (2004) Serum proteomic profiles suggest celecoxibmodulated targets and response predictors. Cancer Res. 64:2904–2909.
Breiman, L., Friedman, J.H., Olshen, R.A., and Stone, G.J. (1984) Classification and regression trees. In The Wadsworth Statistics/Probability Series. (Bickel, P., Cleveland, W., and Dudley, R., eds.), Belmont: Wadsworth International Group.
Poon, T.C.W., Chan, A.T.C., Zee, B., Ho, S.K.W., Mok, T.S.K., Leung, T.W.T., et al. (2001) Application of classification tree and neural network algorithm to the identification of serological liver marker profiles in the diagnosis of hepatocellular carcinoma. Oncology 61:275–283.
Markey, M.K., Tourassi, G.D., and Floyd Jr, C.E. (2003) Decision tree classification of proteins identified by mass spectrometry of blood serum samples from people with and without lung cancer. Proteomics 3:1678–1679.
Chan, A.T.C., Teo, P.M.L., Nagan, R.K., Leung, T.W., Lau, W.H., Zee, B., et al. (2002) Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locaregionally advanced nasopharyngeal carcinoma: progression free survival analysis of a phase III randomized trial. J. Clin. Oncol. 20:2038–2044.
Radmacher, M.D., McShane, L.M., and Simon, R. (2002) A paradigm for class prediction using gene expression profiles. J. Comput. Biol. 9:505–511.
Al-Sarraf, M., LeBlanc, M., Giri, P.G. Fu, K.K., Cooper, J., Vuong, T., et al. (1998) Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. J. Clin. Oncol. 16:1310–1317.
Chan, A.T.C., Lo, Y.M.D., Zee, B., Chan, L.Y.S., Ma, B.B.Y., Leung, S.F., et al. (2002) Plasma Epstein-Barr virus DNA and residual disease after radiotherary after radiotherapy for undifferentiated carcinoma. J. Natl. Cancer. Inst. 94:1614–1619.
Diamandis, E.P. (2003) Proteomic patterns in biological fluids: do they represent the future of diagnostics? Clin. Chem. 49:1272–1275.
Diamandis, E.P. (2004) Analysis of serum proteomic patterns for early cancer diagnosis: drawing attention to potential problems. J. Natl. Cancer Inst. 96:353–256.
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Poon, T.C.W., Chow, S.M., Ma, B.B.Y. et al. Serum proteomic pattern for predicting recurrence of undifferentiated nasopharyngeal carcinoma after radiotherapy. Clin Proteom 1, 365–373 (2004). https://doi.org/10.1385/CP:1:3-4:365
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DOI: https://doi.org/10.1385/CP:1:3-4:365