Lectin microarray technology identifies specific lectins related to lymph node metastasis of advanced gastric cancer

Abstract

Background Although various molecular profiling technologies have the potential to predict specific tumor phenotypes, the comprehensive profiling of lectin-bound glycans in human cancer tissues has not yet been achieved. Methods We examined 242 advanced gastric cancer (AGC) patients without or with lymph node metastasis-N0 (n = 62) or N? (n = 180)-by lectin microarray, and identified the specific lectins highly associated with AGC phenotypes. Results In seven gastric cancer cell lines, in contrast to expressed-in-cancer lectins, not-expressed-in-cancer (NEC) lectins were tentatively designated by lectin microarray. Binding signals of the specific lectins were robustly reduced in AGC patients with N? status as compared with those with N0 status. The receiver operating characteristic curve determined the optimal cutoff value to differentiate N0 status from N? status, and subsequent profiling of NEC lectins identified Vicia villosa agglutinin (VVA) association with the significant other lectins involved in lymph node metastasis. VVA reaction was clearly found on cancer cells, suggesting that it may result from carcinoma-stroma interaction in primary AGC, because VVA is an NEC lectin. Most intriguingly, VVA reaction was remarkably attenuated in the tumor cells of the metastatic lymph nodes, even if it was recognized in primary AGC. In AGC, histological type was strongly associated with soybean agglutinin and Bauhinia purpurea lectin, whereas p53 mutation was the best correlated with Griffonia simplicifolia lectin II. Conclusions Lectin microarrays can be used to very accurately quantify the reaction of glycans with tumor tissues, and such profiles may represent the specific phenotypes, including N? status, histological type, or p53 mutation of AGC.

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

“…In this way, the density and natural orientation of glycans attached to the protein core are kept in their native form . Recently, lectin microarray has been recognized as a diagnostic tool for glycoprofiling of different types of carcinoma such as non‐small cell lung carcinoma, CRC, gastric, and prostate cancer…”

Plant Lectins Targeting O-Glycans at the Cell Surface as Tools for Cancer Diagnosis, Prognosis and Therapy

“…Low binding of BPL, the T/Tn-specific Bauhinia purpurea lectin, was identified as a predictive factor for the recurrence of gastric cancer in gastrectomized patients ( n = 60), in association to lymph node metastasis [135]. An attenuated VVA ( Vicia villosa agglutinin) binding to metastatic lymph node cells was also observed in advanced gastric cancer as compared to the strong recognition of the lectin by primary advanced gastric cancer cells [136]. In addition, the histological type of advanced gastric cancer was strongly associated with the binding of soybean lectin (SBA) and Bauhinia purpurea lectin (BPL), except for the p53 mutations which correlate well with the Griffonia simplicifolia lectin II (GSA).…”

Role of lectin microarrays in cancer diagnosis

“…Particular interest has been in the use of lectins for the detection of glycosylation patterns in patient samples of different cancers. Lectin microarrays have been recently described for the glycomic profiling of non‐small cell lung carcinoma , colorectal , gastric , and prostate cancer . A large part of the clinically approved and potential new cancer markers are glycoproteins.…”