Multi-omics analysis of LAMB3 as a potential immunological and biomarker in pan-cancer

Yanghao Wang; Guoyu Li; ZhiYuan Wang; Weizhou Wang; Xiaofang Wang; Xuan Luo; Juan Zhao; Fangfang Li; Li Bian

doi:10.3389/fmolb.2023.1157970

Multi-omics analysis of LAMB3 as a potential immunological and biomarker in pan-cancer

Front Mol Biosci. 2023 Jul 27:10:1157970. doi: 10.3389/fmolb.2023.1157970. eCollection 2023.

Authors

Yanghao Wang¹, Guoyu Li¹, ZhiYuan Wang¹, Weizhou Wang², Xiaofang Wang³, Xuan Luo¹, Juan Zhao¹, Fangfang Li¹, Li Bian¹

Affiliations

¹ Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
² Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
³ Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Abstract

Laminin Subunit Beta 3 (LAMB3) is a transcription factor and participates in the coding of laminin. It plays an important role in cell proliferation, adhesion, and transfer by regulating various target genes and signaling pathways. However, the role of LAMB3 in human pan-cancer immunology and prognosis is still poorly understood. The TCGA, GTEx, CCLE, and HPA databases were utilized for the analysis of LAMB mRNA and protein expression. The expression of LAMB3 in various immune and molecular subtypes of human cancer was examined using the TISIDB database. The prognostic significance of LAMB3 in various cancers and clinical subtypes was investigated using Kaplan-Meier and Cox regression analysis. The relationship between LAMB3 expression, various immune cell infiltration, immune checkpoints, tumor mutational load, microsatellite instability, and DNA methylation was examined using the TCGA database. Clinical samples of four lung cancer cell lines and eight lung cancer cases were collected to confirm the expression of mRNA in lung cancer. In 17 cancers, the mRNA for LAMB3 is expressed differently and has good diagnostic and prognostic value in 22 cancers. Cox regression and Nomogram analysis show that LAMB3 is an independent risk factor for 15 cancers. LAMB3 is implicated in a variety of tumorigenesis and immune-related signaling pathways, according to GO, KEGG, and GSEA results. LAMB3 expression was associated with TMB in 33 cancer types and MSI in 32 cancer types, while in lung cancer LAMB3 expression was strongly associated with immune cell infiltration and negatively correlated with all seven methylated CpG islands. Cellular experiments demonstrated that LAMB3 promotes malignant behavior of tumor cells. Preliminary mechanistic exploration revealed its close association with PD-L1, CTLA4, cell stemness gene CD133 and β-catenin-related signaling pathways. Based on these findings, it appears that LAMB3 could be a potential therapeutic target for immunotherapy and tumor prognosis. Our findings reveal an important role for LAMB3 in different cancer types.

Keywords: LAMB3; biomarker; multi-omics; pan-cancer; tumor immunity.

Grants and funding

This work was supported by the Regional Fund Project of the National Natural Science Foundation of China (82060423), the Regional Fund Project of the National Natural Science Foundation of China (82060496), Yunnan Provincial Department of Science and Technology-Kunming Medical University applied basic research joint special major project (202001AY0700 1-007), Yunnan Provincial Education Department Scientific Research Fund (2023Y0786) and Kunming Medical University Student Innovation and Entrepreneurship Training Program Project (202210678018).