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脂肪细胞对胃癌进展的影响:预后见解与分子特征

Adipocytes impact on gastric cancer progression: Prognostic insights and molecular features.

作者信息

Shang Jia-Rong, Zhu Jin, Bai Lu, Kulabiek Delida, Zhai Xiao-Xue, Zheng Xia, Qian Jun

机构信息

Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China.

出版信息

World J Gastrointest Oncol. 2024 Jul 15;16(7):3011-3031. doi: 10.4251/wjgo.v16.i7.3011.

Abstract

BACKGROUND

Adipocytes, especially adipocytes within tumor tissue known as cancer-associated adipocytes, have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer (GC). Their influence on tumor progression and patient prognosis has sparked significant interest in recent research. The main objectives of this study were to investigate adipocyte infiltration, assess its correlation with clinical pathological features, develop a prognostic prediction model based on independent prognostic factors, evaluate the impact of adipocytes on immune cell infiltration and tumor invasiveness in GC, and identify and validate genes associated with high adipocyte expression, exploring their potential diagnostic and prognostic value.

AIM

To explore the relationship between increased adipocytes within tumor tissue and prognosis in GC patients as well as the associated mechanisms and potential biomarkers, using public databases and clinical data.

METHODS

Using mRNA microarray datasets from the Gene Expression Omnibus database and clinical samples from Jiangsu Provincial Hospital, survival and regression analyses were conducted to determine the relevant prognostic factors in GC. Feature gene selection was performed using least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms, followed by differential gene expression analysis, gene ontology, pathway analysis, and Gene Set Enrichment Analysis. Immune cell infiltration was analyzed using the CIBERSORT algorithm.

RESULTS

Tumor adipocyte infiltration correlated with poor prognosis in GC, leading to the development of a highly accurate and discriminative prognostic prediction model. Key genes, , , , and , were identified as associated with high adipocyte expression in GC. The diagnostic and prognostic potential of these identified genes was validated using independent datasets. Downregulation of immune cells was observed in GC with high adipocyte expression.

CONCLUSION

GC with high intratumoral adipocyte expression demonstrated aggressive tumor biology and a poorer prognosis. The genes , , , and have been identified as holding diagnostic and prognostic significance in GC. These findings strongly support the use of adipocyte expression as a valuable indicator of tumor invasiveness and anticipated patient outcomes in GC.

摘要

背景

脂肪细胞,尤其是肿瘤组织内被称为癌症相关脂肪细胞的脂肪细胞,在胃癌(GC)的肿瘤微环境中的关键作用已越来越受到认可。它们对肿瘤进展和患者预后的影响在最近的研究中引发了极大兴趣。本研究的主要目的是调查脂肪细胞浸润情况,评估其与临床病理特征的相关性,基于独立预后因素建立预后预测模型,评估脂肪细胞对GC中免疫细胞浸润和肿瘤侵袭性的影响,以及鉴定和验证与高脂肪细胞表达相关的基因,探索其潜在的诊断和预后价值。

目的

利用公共数据库和临床数据,探讨肿瘤组织内脂肪细胞增多与GC患者预后之间的关系以及相关机制和潜在生物标志物。

方法

使用来自基因表达综合数据库的mRNA微阵列数据集和江苏省人民医院的临床样本,进行生存分析和回归分析以确定GC中的相关预后因素。使用最小绝对收缩和选择算子以及支持向量机递归特征消除算法进行特征基因选择,随后进行差异基因表达分析、基因本体分析、通路分析和基因集富集分析。使用CIBERSORT算法分析免疫细胞浸润情况。

结果

肿瘤脂肪细胞浸润与GC的不良预后相关,从而建立了一个高度准确且具有鉴别力的预后预测模型。关键基因 、 、 、 和 被鉴定为与GC中高脂肪细胞表达相关。使用独立数据集验证了这些鉴定出的基因的诊断和预后潜力。在高脂肪细胞表达的GC中观察到免疫细胞下调。

结论

肿瘤内脂肪细胞高表达的GC表现出侵袭性的肿瘤生物学行为和较差的预后。基因 、 、 、 和 已被鉴定在GC中具有诊断和预后意义。这些发现有力地支持了将脂肪细胞表达用作GC中肿瘤侵袭性和预期患者预后的有价值指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5378/11271780/9299da7faf0f/WJGO-16-3011-g001.jpg

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