宫颈癌自噬相关基因和免疫浸润的综合分析。
Comprehensive analysis of autophagy associated genes and immune infiltrates in cervical cancer.
发表日期:2024
作者:
Shuzhen Li, Kun Gao, Desheng Yao
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
宫颈癌(CC)是最常见的妇科恶性肿瘤,也是女性癌症相关死亡的第四大原因。 CC的进展明显受到自噬的影响。我们的目的是利用生物信息学分析来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 Gene 中鉴定了一组自噬相关差异表达基因 (ARDEG)表达式综合 (GEO) 数据库。 ARDEG 通过人类蛋白质图谱 (HPA)、GSE52903 和 GSE39001 数据集进一步验证。 Hub 基因是由 STRING 网络和 Cytoscape 发现的。我们进行了基因集富集分析(GSEA)、基因本体分析(GO)、京都基因和基因组百科全书(KEGG)分析和免疫浸润分析,以进一步了解枢纽基因的功能。采用Kaplan-Meier(K-M)和受试者工作特征(ROC)检查hub基因,共有10个上调(CXCR4、BAX、SPHK1、EIF2AK2、TBK1、TNFSF10、ITGB4、CDKN2A、IL24和BIRC5)鉴定出 19 个下调的 ARDEG(PINK1、ATG16L2、ATG4D、IKBKE、MLST8、MAPK3、ERBB2、ULK3、TP53INP2、MTMR14、BNIP3、FOS、CCL2、FAS、CAPNS1、HSPB8、PTK6、FKBP1B 和 DNAJB1)。 ARDEG 在细胞生长、细胞凋亡、人乳头瘤病毒感染和细胞因子介导方面富集。然后,我们发现 MAPK3 的低表达与 CC 患者的不良预后相关,并且在免疫通路中显着富集。此外,MAPK3的表达与巨噬细胞、B细胞、肥大细胞活化和癌症相关成纤维细胞的浸润水平显着正相关。此外,MAPK3与LGALS9呈正相关,与CTLA4和CD40呈负相关。我们的研究结果表明,MAPK3可以作为新的预后生物标志物来预测CC患者的预后。
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.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.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.Our results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.