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预后生物标志物TUBA1C与肺腺癌肿瘤微环境中的免疫细胞浸润相关。

Prognostic biomarker TUBA1C is correlated to immune cell infiltration in the tumor microenvironment of lung adenocarcinoma.

作者信息

Bian Tingting, Zheng Miaosen, Jiang Daishan, Liu Jian, Sun Hui, Li Xiaoli, Liu Lei, Zhang Jianguo, Liu Yifei

机构信息

Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

School of Medicine, Nantong University, Nantong, Jiangsu, China.

出版信息

Cancer Cell Int. 2021 Mar 2;21(1):144. doi: 10.1186/s12935-021-01849-4.

Abstract

BACKGROUND

TUBA1C is a microtubule component that is involved in a variety of cancers. Our main objective was to investigate TUBA1C expression, its prognostic value, its potential biological functions, and its impact on the immune system of patients with lung adenocarcinoma (LUAD).

METHODS

The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Immunohistochemistry Analysis were used to analyze TUBA1C expression, its clinicopathology, overall survival (OS), and disease-free survival (DFS) in LUAD patients. We also determined the correlation between TUBA1C and tumor-infiltrating immune cells (TIICs) by using CIBERSORT and GEPIA databases. To determine the expression of TUBA1C in LUAD, we analyzed a collection of immune infiltration levels and cumulative survival of LUAD tissues in TIMER database. By using UALCAN, STRING, and GeneMANIA databases, we investigated the protein-coding genes related to TUBA1C and its co-expression genes in LUAD tissues. Gene set enrichment analysis (GSEA) was performed by using the TCGA dataset.

RESULTS

The mRNA and the protein expression of TUBA1C were found to be up-regulated in LUAD tissues. The univariate analysis indicated that an increased expression of TUBA1C was significantly correlated to the following parameters: age, stage, and lymph node metastasis. An over-expression of TUBA1C was associated with a poor prognosis of LUAD. In TIMER and CIBERSORT databases, we found that TUBA1C is correlated with 13 types of TIICs: activated B cell, activated CD4 T cell, central memory CD4 T cell, effector memory CD8 T cell, eosinophils, immature B cell, gamma-delta T cell, immature dendritic cell, mast cell, memory B cell, natural killer T cell, regulatory T cell, and type 2T helper cell. By performing GSEA, we found that TUBA1C is closely correlated to cell cycle, p53 signaling pathway, glycolysis, and gluconeogenesis.

CONCLUSIONS

Our findings indicate that TUBA1C is associated with TIICs in tumor microenvironment. Therefore, it serves as a novel prognostic biomarker and a target for future treatment methods of LUAD.

摘要

背景

TUBA1C是一种参与多种癌症的微管成分。我们的主要目的是研究TUBA1C在肺腺癌(LUAD)患者中的表达、预后价值、潜在生物学功能及其对免疫系统的影响。

方法

使用癌症基因组图谱(TCGA)、基因表达谱交互式分析(GEPIA)和免疫组织化学分析来分析LUAD患者中TUBA1C的表达、其临床病理学、总生存期(OS)和无病生存期(DFS)。我们还通过使用CIBERSORT和GEPIA数据库确定TUBA1C与肿瘤浸润免疫细胞(TIICs)之间的相关性。为了确定TUBA1C在LUAD中的表达,我们在TIMER数据库中分析了LUAD组织的免疫浸润水平和累积生存期。通过使用UALCAN、STRING和GeneMANIA数据库,我们研究了LUAD组织中与TUBA1C相关的蛋白质编码基因及其共表达基因。使用TCGA数据集进行基因集富集分析(GSEA)。

结果

发现TUBA1C的mRNA和蛋白质表达在LUAD组织中上调。单变量分析表明,TUBA蛋白表达增加与以下参数显著相关:年龄、分期和淋巴结转移。TUBA1C的过表达与LUAD的不良预后相关。在TIMER和CIBERSORT数据库中,我们发现TUBA1C与13种TIICs相关:活化B细胞、活化CD4 T细胞、中枢记忆CD4 T细胞、效应记忆CD8 T细胞、嗜酸性粒细胞、未成熟B细胞、γδ T细胞、未成熟树突状细胞。肥大细胞、记忆B细胞、自然杀伤T细胞、调节性T细胞和2型辅助性T细胞。通过进行GSEA,我们发现TUBA1C与细胞周期、p53信号通路、糖酵解和糖异生密切相关。

结论

我们的研究结果表明,TUBA1C与肿瘤微环境中的TIICs相关。因此,它可作为一种新的预后生物标志物和LUAD未来治疗方法的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbef/7923461/470e17ea5160/12935_2021_1849_Fig1_HTML.jpg

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