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糖酵解相关基因高表达与肺腺癌预后不良及免疫细胞浸润不足的关系:一项基于生物信息学分析的研究

High expression of glycolysis-related gene in relation to poor prognosis and deficient immune cells infiltration in lung adenocarcinoma: a study based on bioinformatics analysis.

作者信息

Yu Haoda, Yu Zhen, Qin Chu, Bian Tao, Shi Minhua

机构信息

Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Department of Pulmonary and Critical Care Medicine, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.

出版信息

J Thorac Dis. 2022 Sep;14(9):3488-3499. doi: 10.21037/jtd-22-1043.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is the most important subtype of lung cancer and usually metastasizes. Patients with LUAD usually had a poor prognosis. Identifying viable molecular markers for diagnostic and prognostic prediction among individuals with LUAD is critical for the future management of this disease. This study aimed to determine and verify a correlation between the glycolysis-related phosphoglucomutase 2 () gene and dissatisfactory results and deficient infiltration of immune cells in LUAD.

METHODS

The expression of in LUAD and adjoining normal tissues was screened from The Cancer Genome Atlas (TCGA) data and human protein atlas (HPA), and validatied by quantative reverse transcription polymerase chain reaction (qRT-PCR). We examined the correlation between expression and clinicopathologic characteristics (including pathological stage, gender, M stage, smoker, age, N stage, race, and number pack years smoked) by multivariable approaches and Kaplan-Meier survival curves. The proteins network with was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The correlation between expression and infiltration of immune cells, along with the corresponding gene marker sets, was investigated through the Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER) databases. We evaluated the possible correlation between expression and progression-free interval (PFI), disease-specific survival (DSS), and overall survival (OS) in LUAD patients.

RESULTS

Expression of was up-regulated in LUAD tissues (P=0.003). According to the multivariate logistic regression analysis, the elevated expression level of PGM2 exhibited a remarkable correlation with advanced tumor-node-metastasis (TNM) stage, high-grade malignancy, and primary therapeutic outcome . Overexpression of was shown to be correlated with an unfavorable prognosis including OS (P=0.004, HR =1.54), DSS (P=0.003, HR =1.77), and PFI (P=0.003, HR =1.5) in LUAD. The proteins PGM1 and UGP2 were shown to have a significant correlation with . Additionally, was associated with the lack of infiltrating immune cells as well as their associated gene marker sets in LUAD.

CONCLUSIONS

Overexpression of was shown to be associated with the progression and an unfavorable prognosis of LUAD, as well as with inefficient immune cell infiltration. was expected to be a potential biological marker for predicting the prognosis of patients with LUAD.

摘要

背景

肺腺癌(LUAD)是肺癌最重要的亚型,通常会发生转移。LUAD患者的预后通常较差。识别LUAD个体中用于诊断和预后预测的可行分子标志物对于该疾病的未来管理至关重要。本研究旨在确定并验证糖酵解相关的磷酸葡萄糖变位酶2(PGM2)基因与LUAD中免疫细胞浸润不足和预后不良之间的相关性。

方法

从癌症基因组图谱(TCGA)数据和人类蛋白质图谱(HPA)中筛选LUAD及相邻正常组织中PGM2的表达,并通过定量逆转录聚合酶链反应(qRT-PCR)进行验证。我们通过多变量分析方法和Kaplan-Meier生存曲线研究了PGM2表达与临床病理特征(包括病理分期、性别、M分期、吸烟者、年龄、N分期、种族和吸烟包年数)之间的相关性。使用基因相互作用检索工具(STRING)数据库构建了与PGM2相关的蛋白质网络。通过基因表达谱交互分析(GEPIA)和肿瘤免疫评估资源(TIMER)数据库研究了PGM2表达与免疫细胞浸润及其相应基因标志物集之间的相关性。我们评估了PGM2表达与LUAD患者无进展生存期(PFI)、疾病特异性生存期(DSS)和总生存期(OS)之间的可能相关性。

结果

PGM2在LUAD组织中的表达上调(P = 0.003)。根据多变量逻辑回归分析,PGM2表达水平升高与晚期肿瘤-淋巴结-转移(TNM)分期、高分级恶性肿瘤和主要治疗结果显著相关。PGM2的过表达与LUAD中包括OS(P = 0.004,HR = 1.54)、DSS(P = 0.003,HR = 1.77)和PFI(P = 0.003,HR = 1.5)在内的不良预后相关。蛋白质PGM1和UGP2与PGM2显示出显著相关性。此外,PGM2与LUAD中免疫细胞浸润及其相关基因标志物集的缺乏有关。

结论

PGM2的过表达与LUAD的进展、不良预后以及免疫细胞浸润效率低下有关。PGM2有望成为预测LUAD患者预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f0/9562504/8431a4fdea00/jtd-14-09-3488-f1.jpg

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