基于生物信息学分析LAD1对乳腺癌的预后预测及募集肿瘤相关巨噬细胞作用的研究

Bioinformatic analysis of the roles of LAD1 in predicting breast cancer prognosis and the recruitment of tumor-associated macrophages

目的探讨LAD1基因在乳腺癌中的表达,以及其与肿瘤相关巨噬细胞的募集作用,进一步分析LAD1作为潜在乳腺癌生物标志物的诊断和预后预测价值。方法利用TIMER 2.0数据库分析LDA1基因在各种癌症中的表达水平;通过癌症基因组图谱(TCGA)数据库的数据挖掘,分析乳腺癌组织和正常乳腺组织中LAD1 mRNA的表达差异,以及年龄≤65岁和年龄>65岁乳腺癌患者LAD1 mRNA表达水平;通过人类蛋白质谱查询检索了乳腺癌组织和正常乳腺组织的LAD1的免疫组化染色结果;最后,本研究还评估高风险组和低风险组之间的肿瘤微环境中免疫细胞浸润情况。结果LAD1蛋白在乳腺癌组织中表达明显高于正常乳腺组织,差异有统计学意义(P<0.01);通过TCGA数据库分析,LAD1 mRNA在乳腺癌组织样本中高表达,且年龄≤65岁的乳腺癌患者的LAD1 mRNA表达量相对年龄>65岁乳腺癌患者更高,差异有统计学意义(P<0.05);通过免疫组化提示LDA1蛋白在乳腺癌患者样本中表达量高;最后,运用CIBERSORT算法和京都基因和基因数据库富集分析提示高表达LAD1基因在乳腺癌免疫微环境中与M2型巨噬细胞的表达呈正相关,且差异有统计学意义(P<0.05)。结论本研究揭示了LAD1在乳腺癌中的重要作用,并与TAMs的募集机制相关联。LAD1的表达可能作为一个有效的生物标志物,用于乳腺癌的预后预测。

Objective To investigate the expression of LAD1 gene in breast cancer and its role in the recruitment of tumor-associated macrophages,and further analyze the diagnostic and prognostic values of LAD1 as a potential biomarker of breast cancer.Methods The TIMER 2.0 database was utilized to examine the expression levels of the LAD1 gene across various cancers.By delving into The Cancer Genome Altas(TCGA)database,we evaluated the differential expression of LAD1 mRNA between breast cancer tissues and normal breast tissues.Additionally,we compared the LAD1 mRNA expression between breast cancer patients aged≤65 years and those aged>65 years.Results from the immunohi-stochemical staining of LAD1 in both breast cancer and normal tissues were obtained via queries to the Human Protein Atlas.This study also investigated the disparities in immune cell infiltration within the tumor microenvironment between high-risk and low-risk groups.Results The expression of the LAD1 protein in breast cancer tissues is notably elevated compared to normal breast tissues,with the difference being statistically significant(P<0.01).Analysis from the TCGA database revealed that LAD1 mRNA is highly expressed in breast cancer tissue samples.Notably,breast cancer patients aged≤65 years exhibited higher LAD1 mRNA expression than those aged over 65 years,and this difference was statistically significant(P<0.05).Immunohistochemical assessments further confirmed the elevated expression of LAD1 protein in breast cancer patient samples.Lastly,utilizing the CIBERSORT algorithm and KEGG enrichment analysis,it was deduced that the elevated expression of the LAD1 gene is positively correlated with the presence of M2 macrophages in the breast cancer immune microenvironment,with this association being statistically significant(P<0.05).Conclusion This study underscores the pivotal role of LAD1 in breast cancer,particularly in relation to the recruitment mechanisms of TAMs.LAD1 expression could potentially serve as a valuable prognostic biomarker for breast cancer prognosis prediction.