J. Cancer Mol. 3: 175-181, 2008

[Research Paper] 

Serum Levels of Apolipoprotein A-II as a Potential Marker for Cholangiocarcinoma

Xiaomin Wang, Anjian Xu, Bo Liu, Juling Wang, Liyun Liu, Songwei Dai, Xueyuan Xiao, and Dacheng He

Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, Beijing, China; Department of Thoracic Surgery, General Hospital of Beijing Unit, PLA, Beijing, China

Abstract:

AIM: Cholangiocarcinoma (CC) is a devastating neoplasm usually hard to get diagnosed in the early stage due to the unfavorable anatomic location.  The currently used tumor markers like CEA and CA 19-9 are not always helpful because of the unsatisfactory sensitivities and specificities.  In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was used to identify the potential biomarker for CC.

METHODS: Serum samples from 59 CC patients, 91 esophagus cancer patients, 60 prostate cancer patients, 68 ovarian cancer patients, 61 benign diseases of hepatobiliary system, and 51 normal individuals were analyzed by SELDI-TOF-MS.  The results were further identified and confirmed by Western blot, immunodepletion and ELISA. 

RESULTS: An 8.9-km/z species was detected by SELDI-TOF-MS, which was significantly increased in CC but not other cancers to be distinguishable from the normal control.  The 8.9-km/z species was identified as apolipoprotein A-II (ApoA-II) by tandem mass spectrometry, and further validated by Western blot and immunodepletion analyses.  Furthermore, the ApoA-II levels of serum samples were analyzed by ELISA.  The results were consistent with those obtained by SELDI-TOF-MS.  The levels of ApoA-II in CC patients were remarkably higher than those in normal controls (mean OD value: 0.57 ± 0.20 vs. 0.31 ± 0.12, P < 0.01).  In addition, the immuohistochemistry indicated that ApoA-II displayed some expression at protein level in CC tissues.

CONCLUSION: Serum levels of ApoA-II were significantly elevated in CC but not other cancer types like esophagus and ovarian cancers.  The combination use of ApoA-II with CA 19-9 as efficient biomarkers for CC has been preliminarily tested and discussed in this work.

(Keywords: apolipoprotein A-II; tumor marker; SELDI-TOF; proteomics; cholangiocarcinoma)

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Received 11/23/07; Revised 12/21/07; Accepted 12/22/07.

¹Correspondence: Dr. Xueyuan Xiao or Dr. Dacheng He, Key Laboratory of Cell Proliferation and Regulation of Ministry of Education,

Beijing Normal University, 19^th Xinjiekouwai Street, Beijing 100875, China. Fax: 86-10-58809729. E-mail: dhe@bnu.edu.cn

²Abbreviations: SELDI-TOF-MS, surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry; CC,

cholangiocarcinoma; ApoA-II, apolipoprotein A-II; HDL, high-density lipoprotein.

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Comment on this paper (received on 1/24/2008)