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胃腺癌中NCAPG与肿瘤微环境及肿瘤干性的相互作用特征分析

Characterizing the Crosstalk of NCAPG with Tumor Microenvironment and Tumor Stemness in Stomach Adenocarcinoma.

作者信息

Xiang Zheng, Cha Genlan, Wang Yihao, Gao Jikai, Jia Jianguang

机构信息

Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000.

Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China 233000.

出版信息

Stem Cells Int. 2022 Oct 3;2022:1888358. doi: 10.1155/2022/1888358. eCollection 2022.

DOI:10.1155/2022/1888358
PMID:36238529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9551677/
Abstract

BACKGROUND

Nonstructural maintenance of non-SMC condensin I complex subunit G (NCAPG) exerts critical effects on cancer progression. However, its biological roles in tumorigenesis and metastasis remain unclear. Thus, we aimed to assess the prognostic utility of NCAPG in stomach adenocarcinoma (STAD) and its potential as a tumor biomarker.

METHODS

Pan-cancer expression profile dataset from public databases and corresponding clinical information were extracted. Single-sample gene set enrichment analysis (ssGSEA) was performed for the evaluation of immune correlations pan-cancer. Subsequently, we focused on STAD and evaluated the methylation profiles, copy number variants (CNVs), and single nucleotide variants (SNVs). Immune features were analyzed between high and low NCAPG expression groups. Differential analysis was performed between high and low expression groups to identify differentially expressed genes (DEGs). Prognostic DEGs were screened by univariate analysis, and an NCAPG-based risk model was constructed based on the prognostic DEGs and LASSO analysis.

RESULTS

NCAPG expression in STAD was significantly and positively correlated with four immune checkpoints, namely, CTLA4, PDCD1, LAG3, and CD276, but was negatively correlated with the infiltration of most immune cells. High and low NCAPG expression groups had differential overall survival, tumor mutation burden, and differential enrichment of therapeutic-related pathways. An immune risk scoring model related to NCAPG expression and immune score was constructed which showed a favorable performance in predicting STAD prognosis as well as predicting the response to immunotherapy. In addition, we found a higher mRNA stemness index (mRNAsi) in the high-risk group and a positive correlation between NCAPG expression and mRNAsi.

CONCLUSION

NCAPG was suggested to be involved in the regulation of tumor microenvironment in STAD. High NCAPG expression was related to high tumor stemness and good prognosis. The immune risk model had a potential to predict STAD prognosis and help directing therapeutic treatment.

摘要

背景

非结构性维持非SMC凝聚素I复合物亚基G(NCAPG)对癌症进展具有关键影响。然而,其在肿瘤发生和转移中的生物学作用仍不清楚。因此,我们旨在评估NCAPG在胃腺癌(STAD)中的预后价值及其作为肿瘤生物标志物的潜力。

方法

从公共数据库中提取泛癌表达谱数据集及相应的临床信息。进行单样本基因集富集分析(ssGSEA)以评估泛癌的免疫相关性。随后,我们聚焦于STAD,评估甲基化谱、拷贝数变异(CNV)和单核苷酸变异(SNV)。分析高、低NCAPG表达组之间的免疫特征。对高、低表达组进行差异分析以鉴定差异表达基因(DEG)。通过单变量分析筛选预后DEG,并基于预后DEG和LASSO分析构建基于NCAPG的风险模型。

结果

STAD中NCAPG表达与四个免疫检查点,即CTLA4、PDCD1、LAG3和CD276显著正相关,但与大多数免疫细胞的浸润呈负相关。高、低NCAPG表达组在总生存期、肿瘤突变负担以及治疗相关通路的差异富集方面存在差异。构建了与NCAPG表达和免疫评分相关的免疫风险评分模型,该模型在预测STAD预后以及预测免疫治疗反应方面表现良好。此外,我们发现高危组中mRNA干性指数(mRNAsi)较高,且NCAPG表达与mRNAsi呈正相关。

结论

提示NCAPG参与STAD肿瘤微环境的调节。高NCAPG表达与高肿瘤干性和良好预后相关。免疫风险模型有潜力预测STAD预后并有助于指导治疗。

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