PLA2G2A在肾乳头状细胞癌中的表达及临床意义

doi:10.3969/j.issn.1674-8115.2023.02.003

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (2): 152-161.doi: 10.3969/j.issn.1674-8115.2023.02.003

• 论著 · 基础研究 • 上一篇

PLA2G2A在肾乳头状细胞癌中的表达及临床意义

李芳¹(), 李凯杨¹(), 王珏¹, 晏睿阳¹, 沈慧¹, 刘敏²()

^1.延安大学医学院基础医学院，延安 716000
^2.延安大学附属医院肿瘤科，延安 716000

收稿日期:2022-08-26 接受日期:2023-01-12 出版日期:2023-02-28 发布日期:2023-02-28
通讯作者: 刘敏 E-mail:18792873198@163.com;ydfylm@163.com
作者简介:李芳（1990—），女，讲师，博士；电子信箱：18792873198@163.com
李芳（1990—），女，讲师，博士；电子信箱：18792873198@163.com
基金资助:
陕西省自然科学基础研究计划(2022JQ-907);陕西省高校科协青年人才托举计划项目(20210309);2022年省级大学生创新创业训练计划项目(S202210719089)

Expression and clinical significance of PLA2G2A in kidney renal papillary cell carcinoma

LI Fang¹(), LI Kaiyang¹(), WANG Jue¹, YAN Ruiyang¹, SHEN Hui¹, LIU Min²()

^1.School of Basic Medicine, Medical School of Yan'an University, Yan'an 716000, China
^2.Department of Oncology, Yan'an University Affiliated Hospital, Yan'an 716000, China

Received:2022-08-26 Accepted:2023-01-12 Online:2023-02-28 Published:2023-02-28
Contact: LIU Min E-mail:18792873198@163.com;ydfylm@163.com
Supported by:
Natural Science Basic Program of Shaanxi Province(2022JQ-907);Shaanxi University Science and Technology Association Youth Talent Promotion Project(20210309);2022 Provincial College Students Innovation and Entrepreneurship Training Program Project(S202210719089)

摘要/Abstract

摘要：

目的·探讨ⅡA组磷脂酶A2（phospholipase A2 group ⅡA，PLA2G2A）在肾乳头状细胞癌（kidney renal papillary cell carcinoma，KIRP）中的表达及临床意义，为寻找KIRP靶向治疗靶点提供新的思路。方法·使用SangerBox在线软件分析PLA2G2A在泛癌中的表达水平及其与泛癌预后、免疫浸润的关系。在此基础上，借助UCSC xena数据库分析PLA2G2A在KIRP中的表达水平，并利用UALCAN数据库和TIMER数据库分别分析PLA2G2A与KIRP患者总生存期和免疫浸润的关系。此外，通过LinkedOmics数据库对KIRP中PLA2G2A进行相关基因分析及基因本体论（Gene Ontology，GO）功能分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）信号通路富集分析。结果·PLA2G2A在包括KIRP在内的15种来自癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库的肿瘤样本组织中呈显著低表达，结合基因型-组织表达（Genotype-Tissue Expression，GTEx）数据库进一步发现PLA2G2A在KIRP中显著低表达。同时研究结果显示，PLA2G2A的表达水平与多种肿瘤的预后及免疫浸润密切相关；且PLA2G2A在KIRP中的表达水平越高，患者预后越差、免疫浸润丰度越高。GO功能分析结果显示：KIRP中PLA2G2A在生物过程（biological process，BP）方面主要富集于生物调节和代谢等过程，在细胞组分（cell component，CC）方面主要富集于细胞膜和细胞核等，在分子功能（molecular function，MF）方面主要富集于蛋白质结合和离子结合等。KEGG信号通路富集显示：与PLA2G2A正相关的通路主要富集于细胞周期、核糖体、蛋白酶体、系统性红斑狼疮、抗原加工和提呈等信号通路；与PLA2G2A负相关的通路主要富集于柠檬酸循环、丙酮酸代谢、碳代谢等信号通路。结论·PLA2G2A在KIRP中呈显著低表达，但其在KIRP中的表达水平越高，患者预后越差、免疫浸润丰度越高；KIRP中PLA2G2A正相关通路主要富集于细胞周期、免疫相关通路（如系统性红斑狼疮、抗原加工和提呈）等，其负相关通路主要富集于柠檬酸循环、丙酮酸代谢等。因此，PLA2G2A在KIRP的发生发展中到底发挥抑癌还是促癌作用，还需进一步深入探究。

关键词: ⅡA组磷脂酶A2, 肾乳头状细胞癌, 泛癌, 预后, 免疫浸润

Abstract:

Objective ·To investigate the expression and clinical significance of phospholipase A2 Group ⅡA (PLA2G2A) in kidney renal papillary cell carcinoma (KIRP), and provide new ideas for seeking KIRP targets. Methods ·The expression level of PLA2G2A in pan-cancer and its relationship with prognosis and immune infiltration were analyzed by online software SangerBox. On this basis, the expression level of PLA2G2A in KIRP was analyzed with the help of the UCSC xena database; the correlation between PLA2G2A expression and prognosis and immune infiltration of KIRP were analyzed by using the UALCAN database and the TIMER database, respectively. In addition, the LinkedOmics database was used to analyze the related genes, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment of PLA2G2A in KIRP. Results ·PLA2G2A was significantly low expressed in 15 tumor samples from The Cancer Genome Atlas (TCGA) including KIRP. It was further validated that PLA2G2A was significantly lower expressed in KIRP with the help of Genotype-Tissue Expression (GTEx) database. The expression level of PLA2G2A was closely related to the prognosis and immune infiltration of various tumors. The higher the expression level of PLA2G2A in KIRP was, the worse the prognosis and the higher the abundance of immune infiltration were. GO analysis showed that PLA2G2A was mainly enriched in biological regulation and metabolic process in biological process (BP), cell membrane and nucleus in cell component (CC), and protein binding and ion binding in molecular function (MF). KEGG pathway enrichment analysis suggested that the pathways positively correlated with PLA2G2A were enriched in ribosome, cell cycle, proteasome, systemic lupus erythematosus and antigen processing and presentation, while the pathways negatively correlated with PLA2G2A were enriched in citrate cycle, pyruvate metabolism, and carbon metabolism. Conclusion ·PLA2G2A is significantly lower expressed in KIRP. Unexpectedly, the higher the expression level of PLA2G2A in KIRP is, the worse the prognosis and the higher the abundance of immune infiltration are. In KIRP, the PLA2G2A positively correlated pathways are mainly enriched in cell cycle and immune-related pathways (such as systemic lupus erythematosus, antigen processing and presentation), while the negatively correlated pathways are mainly concentrated in citric acid cycle and pyruvate metabolism signaling pathways. Thus, it is needed to be further explored whether PLA2G2A plays a role in the development of KIRP as a tumor suppressor or an oncogene.

Key words: phospholipase A2 group ⅡA (PLA2G2A), kidney renal papillary cell carcinoma (KIRP), pan-cancer, prognosis, immune infiltration

中图分类号:

R737.11

李芳, 李凯杨, 王珏, 晏睿阳, 沈慧, 刘敏. PLA2G2A在肾乳头状细胞癌中的表达及临床意义[J]. 上海交通大学学报（医学版）, 2023, 43(2): 152-161.

LI Fang, LI Kaiyang, WANG Jue, YAN Ruiyang, SHEN Hui, LIU Min. Expression and clinical significance of PLA2G2A in kidney renal papillary cell carcinoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 152-161.

图/表 5

图1 PLA2G2A 在泛癌中的表达水平Note：A. The expression levels of PLA2G2A in 26 different types of TCGA tumors. B. The expression levels of PLA2G2A in different types of tumors were analyzed by combining TCGA and GTEx databases. BLCA—bladder urothelial carcinoma; BRCA—breast invasive carcinoma; CESC—cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL—cholangio carcinoma; COAD—colon adenocarcinoma; COADREAD—colorectal adenocarcinoma; ESCA—esophageal carcinoma; GBM—glioblastoma multiforme; GBMLGG—glioma; HNSC—head and neck squamous cell carcinoma; KICH—kidney chromophobe; KIPAN—pan-kidney cohort; KIRC—kidney renal clear cell carcinoma; KIRP—kidney renal papillary cell carcinoma; LGG—brain lower grade glioma; LIHC—liver hepatocellular carcinoma; LUAD—lung adenocarcinoma; LUSC—lung squamous cell carcinoma; PAAD—pancreatic adenocarcinoma; PCPG—pheochromocytoma and paraganglioma; PRAD—prostate adenocarcinoma; READ—rectum adenocarcinoma; STAD—stomach adenocarcinoma; STES—stomach and esophageal carcinoma; THCA—thyroid carcinoma; UCEC—uterine corpus endometrial carcinoma; T—tumor; N—normal.

Fig 1 Expression level of PLA2G2A in pan-cancer

图2 PLA2G2A 的表达水平与泛癌预后关系的生存森林图Note：A. HR(95% CI) for OS. B. HR(95% CI) for DSS. C. HR(95% CI) for PFI. D. HR(95% CI) for DFI.

Fig 2 Survival forest map for prognostic analysis of PLA2G2A expression in pan-cancer

图3 PLA2G2A的表达水平与泛癌免疫浸润的关系Note：A. Relationship between PLA2G2A expression level and abundance of immune cell infiltration. B. Correlation between PLA2G2A expression level and immune infiltration scores for KIRP, KICH, and COADREAD.

Fig 3 Association of PLA2G2A expression level with immune infiltration in pan-cancer

图4 PLA2G2A 在KIRP中的表达水平及其与KIRP预后和免疫浸润的关系Note：A. PLA2G2A expression in KIRP. B. Relationship between PLA2G2A expression level and OS in KIRP patients. C. Correlation between PLA2G2A expression level and infiltration abundance of six immune cells. D. Relationship between infiltration abundance of immune cells and cumulative survival rate in KIRP patients. ①P=0.020, ②P=0.000.

Fig 4 PLA2G2A expression level and its relationship with prognosis and immune infiltration in KIRP

图5 KIRP中 PLA2G2A 相关基因分析及其GO功能分析和KEGG信号通路富集分析Note：A. Volcanic plot of PLA2G2A-related genes in KIRP. B. Heat map of genes positively associated with PLA2G2A in KIRP. C. Heat map of genes negatively associated with PLA2G2A in KIRP. D. GO function analysis of PLA2G2A in KIRP. E. KEGG enrichment pathway positively correlated with PLA2G2A in KIRP. F. KEGG enrichment pathway negatively correlated with PLA2G2A in KIRP.

Fig 5 Analysis of PLA2G2A-related genes in KIRP and the GO function and KEGG signaling pathway enrichment analysis

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PLA2G2A在肾乳头状细胞癌中的表达及临床意义

Expression and clinical significance of PLA2G2A in kidney renal papillary cell carcinoma

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