Protein glycopatterns for natural regulation of microbiota in lung adenocarcinoma

Despite medical advancements, lung cancer remains a leading cause of mortality, necessitating a deeper understanding. Recent studies show that protein glycopatterns and lung microbiome are crucial in lung cancer development, but their relationship in adenocarcinoma remains unexplored. Therefore, this study evaluated protein glycopatterns and microbial changes between lung adenocarcinoma (n = 70) and paracancerous tissues (n = 70) through lectin microarrays and 16S rDNA sequencing. Further, we explored the impact of protein glycopatterns against a decreased abundant microbiota using extracted glycoproteins reflecting high expression protein glycopatterns observed in lung adenocarcinoma tissues. The results demonstrated a significant up-regulation of protein glycopatterns in tumor tissues, including WGA binding to multivalent Sia/(GlcNAc)n (P = 0.0078) and Jacalin binding to T/Tn antigens (P = 0.0313). Meanwhile, two bacterial species of the genus Sphingomonas showed a significant decrease (P < 0.01) in adenocarcinoma as compared to paracancerous tissue. Interestingly, adhesion assay results showed glycoproteins (25-100 μg/ml) with multivalent Sia and (GlcNAc)n structures extracted by WGA-magnetic particle conjugates significantly reduce (P < 0.0001) Sphingomonas mucosissima adhesion and toxicity to lung cancer cells (A-549). The findings indicated that protein glycopatterns could inhibit cancer-instigating oncomicrobes to intercept cancer progression, offering insights into molecular mechanisms driving disease progression and aiding to develop new treatment strategies.