利用醣蛋白質學方法在肺癌血清中鑑定
血清結合珠蛋白的特殊醣基化生物標誌

醣基化是一種常見的蛋白質修飾，並且在目前癌症研究中引起廣泛的興趣。原因是在癌症的進程中，往往會發現有醣基的改變。肺癌是世界上因癌症死亡的主要癌症之一，而且其發現後的5年存活率小於15%。因此在肺癌血清樣品中尋找生物標誌物是相當重要。我們利用蛋白質體學法，如二維電泳，二維差異凝膠電泳等，鑑定出血紅素結合珠蛋白在肺癌血清樣本中表現量異常增高。西方墨點法與AAL凝集素染色也證實表現量與醣基化程度的不同。這些證據證明血紅素結合珠蛋白的岩藻醣基化顯著地在肺癌各亞型血清中增加。此外，質譜也提供血紅素結合珠蛋白岩藻醣基化增加的證據。並且鑑定其N鍵結醣基的結構為三個唾液酸化的三線端醣，其上3臂甘露醣上的乙醯葡萄醣胺帶有1,3連結的岩藻醣。此特殊醣基化形式上面的唾液酸連結更進一步證實為2,6連結，異於一般所見的sialyl Lewis X抗原。這些初步調查結果顯示，血紅素結合珠蛋白的特殊醣基化形式可作為監測肺癌的發展的生物標記。

關鍵字

血紅素結合珠蛋白；肺癌；生物標誌；轉譯後修飾作用； sialyl Lewis X

並列摘要

Glycosylation is a common protein modification that is of interest in current cancer research because altered carbohydrate moieties are often found during cancer progress. Lung cancer is the major cause of cancer death in the world and the survival rate is less than 15%. A search for biomarkers in human lung cancer serum samples using proteomic approaches, e.g., 2-DE and 2-D DIGE, identified haptoglobin as a protein that is expressed more highly in lung cancer serum samples than in normal serum samples. Western blot analysis and AAL lectin staining were used to validate the expression level and the glycan modification of haptoglobin, respectively. The degree of haptoglobin fucosylation was significantly increased in serum samples from subjects with subtypes of lung cancer compared to normal serum samples. In addition, mass spectrometry provided evidence of an increase of haptoglobin fucosylation; the glycan structure was determined to be an α2,6-linked tri-sialylated triantennary glycan containing α1,3-linked fucose attached to the 4-linked position of the 3-arm mannose of N-linked core pentasaccharide, which is different from the common glycoform , sialyl Lewis X. These preliminary findings suggested that the specific glycoform of haptoglobin may be useful as a marker to monitor lung cancer progression.

並列關鍵字

Haptoglobin ； lung cancer ； biomarker ； PTM ； sialyl Lewis X

參考文獻

1. Levin, P. B. B., ed. (2008) World cancer report 2008, International Agency for Research on Cancer, World Health Organiztion, Lyon.

2. Zochbauer-Muller, S., Gazdar, A. F., and Minna, J. D. (2002) Molecular pathogenesis of lung cancer. Annu Rev Physiol 64, 681-708.

5. Bharti, A., Ma, P. C., and Salgia, R. (2007) Biomarker discovery in lung cancer--promises and challenges of clinical proteomics. Mass Spectrom Rev 26, 451-466.

6. Schneider, J. (2006) Tumor markers in detection of lung cancer. Adv Clin Chem 42, 1-41.

7. Patz, E. F., Jr., Campa, M. J., Gottlin, E. B., Kusmartseva, I., Guan, X. R., and Herndon, J. E., 2nd (2007) Panel of serum biomarkers for the diagnosis of lung cancer. J Clin Oncol 25, 5578-5583.

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利用醣蛋白質學方法在肺癌血清中鑑定血清結合珠蛋白的特殊醣基化生物標誌

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