Wang Yanghao, Li Guoyu, Wang ZhiYuan, Wang Weizhou, Wang Xiaofang, Luo Xuan, Zhao Juan, Li Fangfang, Bian Li
Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Front Mol Biosci. 2023 Jul 27;10:1157970. doi: 10.3389/fmolb.2023.1157970. eCollection 2023.
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.
层粘连蛋白β3亚基(LAMB3)是一种转录因子,参与层粘连蛋白的编码。它通过调节各种靶基因和信号通路,在细胞增殖、黏附和转移中发挥重要作用。然而,LAMB3在人类泛癌免疫和预后中的作用仍知之甚少。利用TCGA、GTEx、CCLE和HPA数据库分析LAMB mRNA和蛋白表达。使用TISIDB数据库检测LAMB3在人类癌症各种免疫和分子亚型中的表达。使用Kaplan-Meier和Cox回归分析研究LAMB3在各种癌症和临床亚型中的预后意义。利用TCGA数据库检测LAMB3表达与各种免疫细胞浸润、免疫检查点、肿瘤突变负荷、微卫星不稳定性和DNA甲基化之间的关系。收集四种肺癌细胞系和八例肺癌病例的临床样本,以证实肺癌中mRNA的表达。在17种癌症中,LAMB3的mRNA表达存在差异,在22种癌症中具有良好的诊断和预后价值。Cox回归和列线图分析表明,LAMB3是15种癌症的独立危险因素。根据GO、KEGG和GSEA结果,LAMB3参与多种肿瘤发生和免疫相关信号通路。LAMB3表达在33种癌症类型中与肿瘤突变负荷相关,在32种癌症类型中与微卫星不稳定性相关,而在肺癌中,LAMB3表达与免疫细胞浸润密切相关,与所有七个甲基化CpG岛呈负相关。细胞实验表明LAMB3促进肿瘤细胞的恶性行为。初步机制探索揭示其与PD-L1、CTLA4、细胞干性基因CD133和β-连环蛋白相关信号通路密切相关。基于这些发现,LAMB3似乎可能是免疫治疗和肿瘤预后的潜在治疗靶点。我们的研究结果揭示了LAMB3在不同癌症类型中的重要作用。