Fucosylated Glycans in α1-Acid Glycoprotein for Monitoring Treatment Outcomes and Prognosis of Cancer Patients

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.

Fucosylated α1-acid glycoprotein as a biomarker to predict prognosis following tumor immunotherapy of patients with lung cancer

“…Whereas, enzymatic and molecular analyses of serum α1,3fucosyltransferase both in wild type and FUT6-deficient individuals together with those of fucosylation in AGP revealed that fucosylation of the AGP molecule was carried solely by the FUT6 gene-encoded hepatic α1,3fucosyltransferase, and that no α1,6, α1,2 or α1,4 but only α1,3fucosylated linkage was present in the AGP molecule 22–24 . Furthermore, we developed a MALDI-TOF-MS system with a novel operation software (AGPAS) to analyze glycan structures of AGP comprehensively and determined a relative abundance of α1,3fucosylated glycans with tri- and tetraantennary glycan chains in AGP (FUCAGP) 25,26 . Accordingly, it was found, for the first time, that α1,3fucosylated AGP could be an appropriate marker of disease progression and prognosis in various cancer patients, and that abnormally high levels of FUCAGP were found in patients with esophagus, stomach, lung, breast, liver, pancreas, colon and rectum carcinomas who had a poor prognosis 25,26 .…”

“…Furthermore, we developed a MALDI-TOF-MS system with a novel operation software (AGPAS) to analyze glycan structures of AGP comprehensively and determined a relative abundance of α1,3fucosylated glycans with tri- and tetraantennary glycan chains in AGP (FUCAGP) 25,26 . Accordingly, it was found, for the first time, that α1,3fucosylated AGP could be an appropriate marker of disease progression and prognosis in various cancer patients, and that abnormally high levels of FUCAGP were found in patients with esophagus, stomach, lung, breast, liver, pancreas, colon and rectum carcinomas who had a poor prognosis 25,26 . It was of particular interest that recurrence and/or metastasis occurred in patients who had been undergoing chemotherapies and/or radiation after operation was detected by elevated levels of FUCAGP in advance before their determinations with computerized tomography (CT) scans and diagnoses with conventional tumor markers.…”

Glycan profiling using formalin‐fixed, paraffin‐embedded tissues: Hippeastrum hybrid lectin is a sensitive biomarker for squamous cell carcinoma of the uterine cervix

“…It was an effective study of a disease such as lung cancer for which tissue diagnosis is difficult before treatment . In addition, lectins have been studied as predictors of recurrence and the prognosis . However, the actual roles of lectins and their binding glycoproteins have not been clarified in any research.…”

“…23 In addition, lectins have been studied as predictors of recurrence and the prognosis. 24 However, the actual roles of lectins and their binding glycoproteins have not been clarified in any research. In this study, our results suggested that HHL might be associated with infiltration of SCC, which means it could become a marker of the prognosis or relapse in the future.…”

Host-Microbial Gut Interactions and Mushroom Nutrition

“…In the healthy gut, the resident bacteria occupy intestinal colonization niches. A major function of the commensal microbiota is the proliferation and colonization of incoming enteric pathogens as well as opportunistic pathobionts through multiple mechanisms [10,11].…”