利用泛癌分析SDHB基因在嗜铬细胞瘤和副神经节瘤患者中的作用OACSTPCD
Pan-cancer analysis of the role of SDHB gene in patients with pheochromocytoma and paraganglioma
目的 利用生物信息分析SDHB基因在泛癌中的表达及预后,并深入探索嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)患者中SDHB基因突变导致信号通路的改变以及与免疫浸润的关系.方法 在癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库中分析SDHB基因在泛癌中的表达以及与生存预后的关系.通过分析TCGA数据库和TARGET数据库,了解PPGL患者中SDHB基因突变影响的其他基因的表达变化并对相关性基因进行富集分析和信号通路分析,并探索PPGL患者中SDHB基因表达与免疫细胞浸润的关系.结果 SDHB基因在21种肿瘤组织中的表达高于相应的正常组织,包括膀胱移行细胞癌、乳腺浸润性癌、宫颈鳞状细胞癌和宫颈腺癌、结肠癌、弥漫性大B细胞淋巴瘤、食管癌、多形成性胶质细胞瘤、头颈鳞状细胞癌、脑低级别胶质瘤、肺腺癌、肺鳞状细胞癌、卵巢浆液性囊腺癌、胰腺癌、前列腺腺癌、直肠腺癌、皮肤黑色素瘤、胃腺癌、甲状腺癌、胸腺瘤、子宫内膜癌和子宫肉瘤,差异均有统计学意义(P均<0.01),而在包括PPGL在内的其他7种肿瘤中表达低于正常组织,包括肾上腺皮质癌、胆管癌、肾嫌色细胞癌、肾透明细胞癌、肾乳头状细胞癌、急性髓细胞样白血病和PPGL,差异均有统计学意义(P均<0.01).分析SDHB基因的表达与生存预后的关系,发现在胃腺癌、肾透明细胞癌、间皮瘤、骨肉瘤和肾乳头状细胞癌中,SDHB基因表达降低预示预后不良;而在子宫内膜癌、胶质瘤、头颈鳞状细胞癌、急性髓细胞样白血病、口腔鳞状细胞癌和肾上腺皮质癌中,SDHB基因表达增高预示预后不良.在相关性和富集分析中发现SDHB基因表达主要与神经活性配体-受体相互作用、库欣综合征、皮质醇合成和分泌、肽受体活性、G-蛋白偶联肽受体活性、神经肽受体活性、突触膜内在成分、突触膜组成部分、突触后特化膜组成部分、环核苷酸介导的信号通路、神经肽信号通路、糖皮质激素代谢过程等信号通路相关.在肿瘤免疫浸润分析中发现在SDHB基因低表达组中,浸润性最高的免疫细胞是浆细胞样树突状细胞(pDC)和调节性T细胞(TReg),提示pDC细胞和TReg细胞在PPGL肿瘤患者中发挥一定的作用.结论 SDHB基因在多种肿瘤中存在异常表达,并且与肿瘤的预后有一定的相关性;在PPGL患者中,SDHB基因影响的信号通路和高浸润的免疫细胞为未来的机制研究和免疫治疗提供新的思路.
OBJECTIVE To investigate the expression and prognosis of SDHB gene in pan-cancer by bioinformatics analysis,and to explore SDHB-related genes,potential pathways and immune cell infiltration in pheochromocytoma paraganglioma(PPGL).METHODS The expression of SDHB gene in pan-cancer and its relationship with survival prognosis were analyzed in The Cancer Genome Atlas(TCGA)and genotype-tissue expression(GTEx)databases.The expression changes of other genes affected by SDHB mutations,the enrichment analysis and signaling pathway analysis in PPGL patients were carried out by analyzing the TCGA database and the TARGET database.In addition,the relationship between SDHB expression and immune cell infiltration in PPGL patients was explored.RESULTS Compared with normal tissues,the expression of SDHB in 21 tumors was higher than that in normal tissues(P<0.01):BLCA,BRCA,CESC,COAD,DLBC,ESCA,GBM,HNSCC,LGG,LUAD,LUSC,OV,PAAD,PRAD,READ,SKCM,STAD,THCA,THYM,UCEC and UCS.It was expressed lower than normal in 7 other tumors(P<0.01),including ACC,CHOL,KICH,KIRC,KIRP,LAML and PPGL.The relationship between SDHB expression and survival prognosis was analyzed,and it was found that in STAD,KIRC,MESO,OS,and KIR,lower SDHB expression predicted poor prognosis,while higher expression predicted good prognosis.In UCEC,LGG,HNSCC,LAML,OSCC,and ACC,lower SDHB expression predicted a better prognosis,and similarly,higher expression predicted a poor prognosis.In correlation and enrichment analysis,the expression of SDHB was mainly related to neuroactive ligand-receptor interaction,Cushing's syndrome,cortisol synthesis and secretion,peptide receptor activity,G protein-coupled peptide receptor activity,neuropeptide receptor activity,intrinsic components of the synaptic membrane,components of the synaptic membrane,components of the postsynaptic specialized membrane,cyclic nucleotide-mediated signaling pathways,neuropeptide signaling pathways,glucocorticoid metabolism processes and other signaling pathways.In immune infiltration analysis,it was found that the immune cells with the highest infiltration in the SDHB lower expression group were pDC cells and TReg cells,suggesting that pDC cells and TReg cells may play a certain role in PPGL patients.CONCLUSION SDHB gene is abnormally expressed in a variety of tumors,and it has a certain correlation with the prognosis of tumors.In PPGL patients,the signaling pathways affected by SDHB and highly infiltrating immune cells provide new insights for future mechanistic studies and immunotherapy.
王璞;高立明;张文阳;夏寅
首都医科大学附属北京天坛医院耳鼻咽喉头颈外科,北京 100070首都医科大学附属北京天坛医院耳鼻咽喉头颈外科,北京 100070首都医科大学附属北京天坛医院耳鼻咽喉头颈外科,北京 100070首都医科大学附属北京天坛医院耳鼻咽喉头颈外科,北京 100070
嗜铬细胞瘤副神经节瘤泛癌分析免疫细胞浸润SDHB基因
PheochromocytomaParagangliomapan-cancer analysisimmune cell infiltrationSDHB gene
《中国耳鼻咽喉头颈外科》 2024 (11)
692-697,6
北京市自然科学基金青年项目(7234361)
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