Comprehensive analysis of autophagy associated genes and immune infiltrates in cervical cancer.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/IJBMS.2024.74431.16168

Shuzhen Li, Kun Gao, Desheng Yao

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Abstract

Objectives: Cervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is significantly affected by autophagy. Our objective was to use bioinformatics analysis to explore the expression, prognostic significance, and immune infiltration of autophagy-related genes in CC.

Materials and methods: We identified a set of autophagy-related differentially expressed genes (ARDEGs) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ARDEGs were further validated by The Human Protein Atlas (HPA), GSE52903, and GSE39001 dataset. Hub genes were found by the STRING network and Cytoscape. We performed Gene Set Enrichment Analysis (GSEA), Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis to further understand the functions of the hub genes. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) were used to check the hub genes.

Results: A total of 10 up-regulated (CXCR4, BAX, SPHK1, EIF2AK2, TBK1, TNFSF10, ITGB4, CDKN2A, IL24, and BIRC5) and 19 down-regulated (PINK1, ATG16L2, ATG4D, IKBKE, MLST8, MAPK3, ERBB2, ULK3, TP53INP2, MTMR14, BNIP3, FOS, CCL2, FAS, CAPNS1, HSPB8, PTK6, FKBP1B , and DNAJB1) ARDEGs were identified. The ARDEGs were enriched in cell growth, apoptosis, human papillomavirus infection, and cytokine-mediated. Then, we found that low expression of MAPK3 was associated with poor prognosis in CC patients and was significantly enriched in immune pathways. In addition, the expression of MAPK3 was significantly positively correlated with the infiltration levels of macrophages, B cells, mast cell activation, and cancer-associated fibroblasts. Furthermore, MAPK3 was positively correlated with LGALS9, and negatively correlated with CTLA4 and CD40.

Conclusion: Our results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.

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全面分析宫颈癌的自噬相关基因和免疫浸润。

目的：宫颈癌（CC）是最常见的妇科恶性肿瘤，也是导致女性癌症相关死亡的第四大原因。自噬对宫颈癌的进展有很大影响。我们的目的是利用生物信息学分析探讨自噬相关基因在CC中的表达、预后意义和免疫浸润：我们从癌症基因组图谱（TCGA）和基因表达总库（GEO）数据库中鉴定了一组自噬相关差异表达基因（ARDEGs）。人类蛋白质图谱（HPA）、GSE52903 和 GSE39001 数据集进一步验证了 ARDEGs。通过 STRING 网络和 Cytoscape 发现了枢纽基因。我们进行了基因组富集分析（Gene Set Enrichment Analysis，GSEA）、基因本体分析（Gene ontology analysis，GO）、京都基因组百科全书分析（Kyoto Encyclopedia of Genes and Genomes，KEGG）和免疫浸润分析，以进一步了解枢纽基因的功能。Kaplan-Meier（K-M）和接收者操作特征（ROC）用于检测枢纽基因：结果：共有 10 个上调基因（CXCR4、BAX、SPHK1、EIF2AK2、TBK1、TNFSF10、ITGB4、CDKN2A、IL24 和 BIRC5）和 19 个下调基因（PINK1、ATG16L2、ATG4D、IKBKE、MLST8、MAPK3、ERBB2、ULK3、TP53INP2、MTMR14、BNIP3、FOS、CCL2、FAS、CAPNS1、HSPB8、PTK6、FKBP1B 和 DNAJB1）。这些ARDEGs在细胞生长、细胞凋亡、人乳头瘤病毒感染和细胞因子介导的过程中富集。然后，我们发现MAPK3的低表达与CC患者的不良预后有关，并且在免疫通路中明显富集。此外，MAPK3的表达与巨噬细胞、B细胞、肥大细胞活化和癌相关成纤维细胞的浸润水平呈显著正相关。此外，MAPK3 与 LGALS9 呈正相关，而与 CTLA4 和 CD40 呈负相关：我们的研究结果表明，MAPK3可作为一种新的预后生物标志物来预测CC患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY

CiteScore

4.00

自引率

4.50%

发文量

142

审稿时长

6-12 weeks

期刊介绍： The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.