HSP-90α在乳腺癌中的诊断价值及功能富集分析  

Clinical Significance and Functional Enrichment Analysis of Plasma HSP-90αin Br east Cancer

作　　者：吴佳慧 刘晓萍 俞快 周伯宣 曹玮 熊海蔚[1] 谢玉芬 吴紫云 史青峰 刘志高 蔡祥凯 李映良[1] WU Jia-hui;LIU Xiao-ping;YU Kuai;ZHOU Bo-xuan;CAO Wei;XIONG Hai-wei;XIE Yu-fena;WU Zi-yun;SHI Qing-feng;LIU Zhi-gao;CAI Xiang-kai;LI Ying-liang(Specialist Breast Center,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;The First Clinical Medical College,Nanchang University,Nanchang 330006,China;Department of Blood Transfusion,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;Jiangxi Provincial Key Laboratory of Blood Transfusion Medicine,Nanchang 330006,China)

机构地区：[1]南昌大学第一附属医院乳腺专病中心 [2]南昌大学第一临床学院 [3]南昌大学第一附属医院输血医学科 [4]输血医学江西省重点实验室,南昌330006

出　　处：《南昌大学学报（医学版）》2024年第6期55-61,共7页Journal of Nanchang University：Medical Sciences

基　　金：国家自然科学基金资助项目(32100729);江西省科技厅重大科技研发专项“揭榜挂帅”制项目(20213AAG01013);江西省主要学科学术和技术带头人培养计划-领军人才项目(20213BCJ22015);江西省科技创新基地计划(20212BCD42006)。

摘　　要：目的探讨血浆HSP-90α水平对乳腺癌的诊断价值及其编码基因HSP90AA1在乳腺癌防治中的作用。方法采用酶联免疫法检测120例乳腺癌患者(乳腺癌组)和84例乳腺良性肿瘤患者(对照组)血浆HSP-90α含量,利用最佳截断值将患者分为HSP-90α表达阳性组和阴性组,分析HSP-90α表达水平与乳腺癌临床病理特征的关系。采用TCGA数据库分析HSP90AA1基因在乳腺癌及正常乳腺组织中的差异表达和对乳腺癌患者预后的影响;采用LinkedOmics进行基因集富集分析。利用TISIDB分析HSP90AA1基因表达与免疫细胞浸润的关系。结果乳腺癌组血浆HSP-90α较对照组显著升高(P<0.0001);血浆HSP-90α含量80.84 ng·mL-1作为乳腺良、恶性肿瘤的截断值,其诊断灵敏度和特异度分为65.83%和77.38%(AUC:0.77;95%CI:0.71~0.83,P<0.01)。HSP-90表达阳性组患者(n=79)较阴性组(n=41)病理分级及高Ki-67指数更高(P<0.05)。HSP90AA1基因在乳腺癌组织中高表达,且HSP90AA1高表达的乳腺癌患者预后更差(P<0.001)。功能分析表明HSP90AA1基因与RNA运输、泛素蛋白酶体途径、细胞周期和细胞周期依赖性激酶1通路密切相关。HSP90AA1基因与肥大细胞(R=-0.35、P<2.2e^(-16))、活化B淋巴细胞(R=-0.31、P<2.2e^(-16))、效应记忆CD8T淋巴细胞(R=-0.30、P<2.2e^(-16))、NK细胞浸润呈负相关(R=-0.26、P=8.01e-19)。结论血浆HSP-90α表达水平可以作为诊断乳腺良恶性肿瘤的良好指标,HSP90AA1基因与多种信号通路调控关系密切,且与免疫细胞浸润相关,可能是乳腺癌防治的重要靶点。Objective To investigate clinical significance of plasma HSP-90αexpression in breast cancer as well as the role of its encoding gene HSP90AA1 in biological processes and prognosis.Methods ELISA was used to detect plasma HSP-90αlevels in 120 breast cancer patients(breast cancer group)and 84 patients with benign breast tumors(control group),and the patients were divided into HSP-90αexpression-positive and-negative groups using the optimal cut-off value to analyze the relationship between the HSP-90αexpression levels and clinicopathological features of breast cancer.The TCGA database was used to analyze the differential expression of HSP90AA1 in breast cancer and normal breast tissues and the effect on the prognosis of breast cancer patients;LinkedOmics was used for gene set enrichment analysis;the relationship between HSP90AA1 expression and immune cell infiltration was analyzed using TISIDB.Results Plasma HSP-90αwas significantly higher in the breast cancer group compared with the control group(P<0.0001);when the cut-off value was set as 80.84 ng·mL-1 for the diagnosis of breast cancer,the diagnostic sensitivity and specificity was 65.83%and 77.38%,respectively(AUC:0.77;95%CI:0.71-0.83,P<0.01).Patients in the HSP-90 expression-positive group(n=79)had higher pathological grading and higher Ki-67 index than those in the negative group(n=41)(P<0.05);the HSP90AA1 gene was highly expressed in breast cancer tissues,and the prognosis of breast cancer patients with high expression of HSP90AA1 was worse(P<0.001).Functional analysis showed that HSP90AA1 was closely associated with RNA transport,ubiquitin proteasome pathway,cell cycle and cell cycle-dependent kinase 1 pathway;HSP90AA1 was negatively correlated with mast cells(R=-0.35,P<2.2e^(-16)),activated B lymphocytes(R=-0.31,P<2.2e^(-16)),effector memory CD8T lymphocytes(R=-0.30,P<2.2e^(-16)),and NK cell infiltration(R=-0.26,P=8.01e-19).Conclusion Plasma HSP-90αexpression level can be used as a good indicator for the diagnosis of malignant breast tumors.The HSP90A

关 键 词：乳腺癌 血浆HSP90α HSP90AA1 诊断 预后 基因集富集分析 

分 类 号：R446.1[医药卫生—诊断学] R453.9[医药卫生—临床医学]