Abstract
One standard treatment option for advanced-stage cancer is surgical resection of malignant tumors following by adjuvant chemotherapy and chemoradiotherapy. Additionally, neoadjuvant chemotherapy may be applied if required. During the time course of treatments, patients are generally followed by computed tomography (CT) surveillance, and by tumor marker diagnosis. However, currently, early evidence of recurrence and/or metastasis of tumors with a clinically relevant biomarker remains a major therapeutic challenge. In particular, there has been no validated biomarker for predicting treatment outcomes in therapeutic settings. Recently, we have looked at glycoforms of serum α1-acid glycoprotein (AGP) by using a crossed affinoimmunoelectrophoresis with two lectins and an anti-AGP antibody. The primary glycan structures of AGP were also analyzed by a mass spectrometer and a novel software in a large number of patients with various cancers. Accordingly, the relative abundance of α1,3fucosylated glycans in AGP (FUCAGP) was found to be significantly high in cancer patients as compared with the healthy controls. Further, strikingly elevated levels of FUCAGP were found in patients with poor prognosis but not in patients with good prognosis. In the current study, levels of FUCAGP in serum samples from various cancer patients were analyzed and 17 patients including 13 who had undergone chemotherapy were followed for several years post operation. FUCAGP level determined diligently by using a mass spectrometer was found to change along with disease prognosis as well as with responses to treatments, in particular, to various chemotherapies. Therefore, FUCAGP levels measured during following-up of the patients after operation appeared to be clinically relevant biomarker of treatment intervention.
Highlights
The occurrence of tumor-associated alteration of glycan structures in glycoproteins and glycolipids expressed on the tumor cell surface, which leads to the secretion of such molecules with aberrant glycans into the plasma as tumor-associated antigens is widely known [1,2]
Tumor-associated antigens in serum samples measured in this study were carcinoembryonic antigen (CEA), cytokelatin 19 fragments (CYFRA), carbohydrate antigen 19–9 (CA 19–9), neuron specific enolase (NSE), squamous cell carcinoma (SCC) and sialyl Lewis X-i (SLX-i)
Low levels of FUCAGP were found in four of the eight patients whose samples were obtained at one day after operation (POD)
Summary
The occurrence of tumor-associated alteration of glycan structures in glycoproteins and glycolipids expressed on the tumor cell surface, which leads to the secretion of such molecules with aberrant glycans into the plasma as tumor-associated antigens is widely known [1,2]. A series of tumor-associated, glycan-based antigens have already been isolated and validated to preferentially predict the presence of tumors in patients, and some have found clinical application as tumor markers, including carcinoembryonic antigen (CEA) [3,4], carbohydrate antigen 19–9 (CA 19–9) [5,6], α-fetoprotein (AFP) [7,8], cancer antigen 125 (CA125) [9,10], sialyl Lewis X-i (SLX-i) [11,12] and sialyl-Tn (STN) [13,14] antigens. Since the level of such antigens secreted from tumors cells into the plasma are not adequate to reach a positive range [20.21], we have been looking for a suitable and reliable new biomarker
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