Background:
Laminin subunit betas (LAMBs) are the major noncollagenous constituent of basement membranes that implicated in biological functions such as cell adhesion, metastasis. However, few studies have systematically analyzed the prognostic value and immune characteristics of LAMBs in pan-cancer types.
Methods:
A pan-cancer comprehensive analysis of LAMBs in expression levels, protein localization, structure, mutations and methylation were explored. Next, Cox regression and Kaplan-Meier method were applied to analyze the prognostic role of LAMBs in pan-cancer. Protein-Protein Interaction (PPI) analysis was performed in the GeneMANIA database, and enrichment analysis was predicted signaling pathways were identifified by using Gene Ontology (GO), Kyoto Encyclopedia of Genes (KEGG) and gene set variation analysis (GSVA) analysis. The immune characteristics of LAMBs in the tumor microenvironment were evaluated via ImmuCellAI and TIMER 2.0. was the main platform to investigate the tumor associated macrophages (TAMs) related to LAMBs in pan-cancer, especially M2-like TAMs. In addition, single-cell sequencing analysis and tracking tumor immunophenotype (TIP) were also conducted to validate the interaction immune role of LAMBs with macrophages in cancers. Furthermore, the immunoregulators, tumour mutational burden (TMB) and microsatellite instability (MSI) was performed to evaluate the immune response role of LAMBs in cancers. Finally, the immunotherapy response and drug sensitive small molecule drugs based on LAMBs expression were predicted.
Results:
The expression, mutation and methylation of LAMBs was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also showed that LAMBs was signifificantly correlated with immune-activated (including pathways and biological processes), immune cell infifiltrations, immunoregulator expressions, TMB and MSI. Importantly, analysis of an independent immunotherapy cohorts revealed that low-risk patients had better immunotherapy responses and prognosis than high-risk patients in some cancers. Furthermore, the immunotherapy response and sensitive small molecule drugs which correlate with LAMBs expression in different cancer types, had a potent capability to predict immunotherapy response in pan-cancers.
Conclusions:
LAMBs expression may contribute to increased infiltration of TAMs, which not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).