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CLC number: R73-34

On-line Access: 2012-12-07

Received: 2012-03-06

Revision Accepted: 2012-06-04

Crosschecked: 2012-10-31

Cited: 4

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Journal of Zhejiang University SCIENCE B 2012 Vol.13 No.12 P.964-971


Combining proteomics, serum biomarkers and bioinformatics to discriminate between esophageal squamous cell carcinoma and pre-cancerous lesion

Author(s):  Xiao-hui Zhai, Jie-kai Yu, Chen Lin, Li-dong Wang, Shu Zheng

Affiliation(s):  Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   zhengshu@zju.edu.cn

Key Words:  Biomarker, Esophageal squamous cell carcinoma, Surface-enhanced laser desorption/ionization, Support vector machine

Xiao-hui Zhai, Jie-kai Yu, Chen Lin, Li-dong Wang, Shu Zheng. Combining proteomics, serum biomarkers and bioinformatics to discriminate between esophageal squamous cell carcinoma and pre-cancerous lesion[J]. Journal of Zhejiang University Science B, 2012, 13(12): 964-971.

@article{title="Combining proteomics, serum biomarkers and bioinformatics to discriminate between esophageal squamous cell carcinoma and pre-cancerous lesion",
author="Xiao-hui Zhai, Jie-kai Yu, Chen Lin, Li-dong Wang, Shu Zheng",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Combining proteomics, serum biomarkers and bioinformatics to discriminate between esophageal squamous cell carcinoma and pre-cancerous lesion
%A Xiao-hui Zhai
%A Jie-kai Yu
%A Chen Lin
%A Li-dong Wang
%A Shu Zheng
%J Journal of Zhejiang University SCIENCE B
%V 13
%N 12
%P 964-971
%@ 1673-1581
%D 2012
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200066

T1 - Combining proteomics, serum biomarkers and bioinformatics to discriminate between esophageal squamous cell carcinoma and pre-cancerous lesion
A1 - Xiao-hui Zhai
A1 - Jie-kai Yu
A1 - Chen Lin
A1 - Li-dong Wang
A1 - Shu Zheng
J0 - Journal of Zhejiang University Science B
VL - 13
IS - 12
SP - 964
EP - 971
%@ 1673-1581
Y1 - 2012
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200066

Objective: biomarker assay is a noninvasive method for the early detection of esophageal squamous cell carcinoma (ESCC). Searching for new biomarkers with high specificity and sensitivity is very important for the early detection of ESCC. Serum surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS) is a high throughput technology for identifying cancer biomarkers using drops of sera. Methods: In this study, 185 serum samples were taken from ESCC patients in a high incidence area and screened by SELDI. A support vector machine (SVM) algorithm was adopted to analyze the samples. Results: The SVM patterns successfully distinguished ESCC from pre-cancerous lesions (PCLs). Also, types of PCL, including dysplasia (DYS) and basal cell hyperplasia (BCH), and healthy controls (HC) were distinguished with an accuracy of 95.2% (DYS), 96.6% (BCH), and 93.8% (HC), respectively. A marker of 25.1 kDa was identified in the ESCC patterns whose peak intensity was observed to increase significantly during the development of esophageal carcinogenesis, and to decrease obviously after surgery. Conclusions: We selected five ESCC biomarkers to form a diagnostic pattern which can discriminate among the different stages of esophageal carcinogenesis. This pattern can significantly improve the detection of ESCC.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Adam, B., Qu, Y., Davis, J.W., Ward, M.D., Clements, M.A., Cazares, L.H., Semmens, O.J., Schellhammer, P.F., Yasui, Y., Ziding, F., et al., 2002. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res., 62(13):3609-3614.

[2]Brockmann, J.G., Nottberg, H., Glodny, B., Sprakel, B., Senninger, N., 2000. Analysis of serum CYFRA 21-1 concentrations in patients with esophageal cancer. Anticancer Res., 20(6D):4899-4904.

[3]Felix, K., Fakelman, F., Hartmann, D., Giese, N.A., Gaida, M.M., Schnolzer, M., Flad, T., Buchler, M.W., Werner, J., 2011. Identification of serum proteins involved in pancreatic cancer cachexia. Life Sci., 88(5-6):218-225.

[4]Handy, B., 2009. The clinical utility of tumor markers. Labmedicine, 40(2):99-103.

[5]Helgason, H.H., Engwegen, J., Zapatka, M., Vincent, A., Cats, A., Boot, H., Beijnen, J.H., Schellens, J.H., 2010. Identification of serum proteins as prognostic and predictive markers of colorectal cancer using surface enhanced laser desorption ionization-time of flight mass spectrometry. Oncol. Rep., 24(1):57-64.

[6]Høgdall, E., Fung, E.T., Christensen, I.J., Yip, C., Nedergaard, L., Engelholm, S.A., Risum, S., Petri, A.L., Lundvall, L., Lomas, L., et al., 2010. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients. Proteom. Clin. Appl., 4(12):940-952.

[7]Hu, Y., Zhang, S.Z., Yu, J.K., Liu, J., Zheng, S., 2005. SELDI-TOF-MS: the proteomics and bioinformatics approaches in the diagnosis of breast cancer. Breast, 14(4):250-255.

[8]Kawaguchi, H., Ohno, S., Miyazaki, M., Hashimoto, K., Egashira, A., Saeki, H., Watanabe, M., Sugimachi, K., 2000. CYFRA 21-1 determination in patients with esophageal squamous cell carcinoma: clinical utility for detection of recurrences. Cancer, 89(7):1413-1417.

[9]Klade, C.S., Voss, T., Krysteck, E., Ahorn, H., Zatloukal, K., Pummer, K., Adolf, G.R., 2001. Identification of tumor antigens in renal cell carcinoma by serological proteome analysis. Proteomics, 1(7):890-898.

[10]Kosugi, S., Nishimaki, T., Kanda, T., Nakagawa, S., Ohashi, M., Hatakeyama, K., 2004. Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma antigen levels in esophageal cancer patients. World J. Surg., 28(7):680-685.

[11]Liu, J., Zheng, S., Yu, J.K., Zhang, J.M., Chen, Z., 2005. Serum protein fingerprinting coupled with artificial neural network distinguishes glioma from healthy population or brain benign tumor. J. Zhejiang Univ. Sci., 6B(1):4-10.

[12]Lu, J.B., Yang, W.X., Zu, S.K., Chang, Q.L., Sun, X.B., Lu, W.Q., Quan, P.L., 1988. Cancer mortality and mortality trends in Henan, China, 1974–1985. Cancer Detect Prev., 13:167-173.

[13]Lu, J.B., Sun, X.B., Dai, D.X., Zu, S.K., Chang, Q.L., 2002. Cancer mortality and mortality trends in Henan Province, China, 1974–1999. Int. J. Cancer, 13:238.

[14]Nakamura, T., Ide, H., Eguchi, R., Hayashi, K., Takasaki, K., Watanabe, S., 1998. CYFRA 21-1 as a tumor marker for squamous cell carcinoma of the esophagus. Dis. Esophagus., 11(1):35-39.

[15]Okamoto, A., Yamamoto, H., Imai, A., Hatakeyama, S., Iwabuchi, I., Yoneyama, T., Hashimoto, Y., Kote, T., Kamimura, N., Mori, K., et al., 2009. Protein profiling of post-prostatic massage urine specimens by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discriminate between prostate cancer and benign lesions. Oncol. Rep., 21(1):73-79.

[16]Opstal-van Winden, A.W., Krop, E.J., Karedal, M.H., Gast, M.C., Lindh, C.H., Jeppsson, M.C., Jonsson, B.A.G., Grobbee, D.E., Peeters, P.H.M., Beijnen, J.H., et al., 2011. Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study. BMC Cancer, 11:381.

[17]Parenti, A., Porzionato, A., Pizzi, S., Guzzardo, V., Fassina, G., Macchi, V., Ninfo, V., de Caro, R., 2007. Expression pattern of squamous cell carcinoma antigen in oesophageal dysplasia and squamous cell carcinoma. Histol. Histopathol., 22(9):989-995.

[18]Parkin, D.M., Bray, F., Ferlay, J., Pisani, P., 2005. Global cancer statistics, 2002. CA Cancer J. Clin., 55(2):74-108.

[19]Petricoin, E.F., Liotta, L.A., 2004. SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer. Curr. Opin. Biotech., 15(1):24-30.

[20]Rai, A., Zhang, Z., Rosenzweig, J., Shih, L., Pham, T., Fung, E., Sokoll, L., Chan, D., 2002. Proteomic approaches to tumor marker discovery. Arch. Pathol. Lab. Med., 126(12):1518-1526.

[21]Rathinam, S., Ward, D.G., James, N.D., Rajesh, P.B., 2011. Proteomic analysis of resectable non-small cell lung cancer: post-resection serum samples may be useful in identifying potential markers. Interact. Cardiovasc. Thorac. Surg., 13(1):3-6.

[22]Tanaka, K., Yano, M., Motoori, M., Kishi, K., Miyashiro, I., Shingai, T., Gotoh, K., Noura, S., Takahashi, H., Ohue, M., et al., 2010. CEA-antigen and SCC-antigen mRNA expression in peripheral blood predict hematogenous recurrence after resection in patients with esophageal cancer. Ann. Surg. Oncol., 17(10):2779-2786.

[23]Tang, K.L., Li, T.H., Xiong, W.W., Chen, K., 2010. Ovarian cancer classification based on dimensionality reduction for SELDI-TOF data. BMC Bioinformatics, 11:109.

[24]Vapnik, V., 1995. The Nature of Statistical Learning Theory. Springer-Verlag, New York.

[25]Wang, L.D., Zheng, S., Liu, B., Zhou, J.X., Li, Y.J., Li, J.X., 2003. CYP1A1, GSTs and mEH polymorphisms and susceptibility to esophageal carcinoma: study of population from a high-incidence area in north China. World J. Gastroenterol., 9(7):1394-1397.

[26]Yamamoto-Ishikawa, K., Suzuki, H., Nezu, M., Kamiya, N., Imamoto, T., Komiya, A., Sogawa, K., Tomonaga, T., Nomura, F., Ichikawa, T., 2009. The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Asian J. Androl., 11(3):299-307.

[27]Yang, C.S., 1980. Research on esophageal cancer in China: a review. Cancer Res., 40(8):2633-2644.

[28]Yilmaz, O., Eroglu, A., Dag, E., Karaoglanoglu, N., Yilmaz, A., 2006. Serum levels of IGF-I and IGFBP-III and their relation with carcinoembryonic antigen and carbohydrate antigen 19-9 in cases of esophageal cancer. Int. J. Clin. Pract., 60(12):1604-1608.

[29]Yu, J.K., Chen, Y.D., Zheng, S., 2004. An integrated approach to the detection of colorectal cancer utilizing proteomics and bioinformatics. World J. Gastroenterol., 10(21):3127-3131.

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