A lectin-based approach to detecting carcinogenesis in breast tissue

Abstract

Abstract. It has been suggested that the diversity of glycosylation structures that form during cancer progression and the sensitivity with which they are able to be detected have great potential for cancer screening. However, the large majority of breast cancer research has instead focused on the development of protein or nucleic acid markers. In the present study, alterations in glycosylation in breast cancer tissue were analyzed using enzyme-linked lectin assays (ELLAs), which have potential for high-throughput screening. Cancer tissues (CCs) and normal tissues (CNs) were collected from women with breast cancer ranging from stage 0 to IIIA. The specimens were divided into two groups, stage 0-I and stage II-III, and the levels of four types of lectin in stage 0-I and stage II-III CCs and CNs were compared by ELLA. The results demonstrated that, relative to CNs, the CCs contained significantly enhanced levels of mannosylation (stage 0-I, P<0.001; stage II-III, P<0.001), galactosylation (stage 0-I, P<0.05; stage II-III, P<0.001), sialylation (stage 0-I, P<0.001; stage II-III, P<0.01) and fucosylation (stage 0-I, P<0.01; stage II-III, P<0.01). Furthermore, stage II-III CCs had higher levels of mannosylation (P<0.05) and galactosylation (P<0.01) than stage 0-I CCs. The sensitivity of the ELLA system ranged from 71-100% when specificity was set at 100%. These results demonstrate that enhanced glycosylation levels identified by ELLA are associated with the development of breast tumors, and provide evidence of the exceptional sensitivity and specificity of the ELLA system in the detection of breast cancer. This approach is anticipated to contribute highly to the development of reliable diagnostic procedures for breast cancer.

Diagnostic Potential of Transferrin Glycoforms—A Lectin‐Based Protein Microarray Approach

“…This finding is also in accordance with the results of Qiu et al . who reported an increase in core fucosylation of several serum proteins due to colon cancer, such as complement C3, histidine‐rich glycoprotein, and kininogen‐1 …”

“…Several hTf glycoforms with terminal Gal were identified by MALDI‐TOF‐MS . ConA is specific for the high‐mannose (Man)‐type structures and hTf is known to possess mostly branched mannosidic structures . Interactions of the moderate intensity were detected between hTf and WGA, specific for N‐acetylglucosamine structures (GlcNAcβ1‐4GlcNAcβ1‐4GlcNAc) and to a lesser extent for Sia .…”

The Diverse Contributions of Fucose Linkages in Cancer

“…FUT8 is the only fucosyltransferase known, to date, to conjugate fucose onto core GlcNAc residues of N-glycans. Extensive studies in melanoma [95], breast [139], liver [63,95,140], ovarian [68], cervical [141] CRC [97,142,143], pancreatic [117], gastrointestinal [89,144,145,146], thyroid papillary [147,148,149], and lung [52,150,151,152] cancers have highlighted core fucosylation and specific core fucosylated proteins as prognostic serum and tissue biomarkers (Table 6).…”

Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study

“…Glycans were also increased in breast cancer tissues compared with normal tissues. Furthermore, stage II and III cancer tissues showed significantly higher glycan expression than stages 0 and I tissues [43].…”