Clinical Significance and Functional Enrichment Analysis of Plasma HSP-90α in Breast Cancer
Objective To investigate clinical significance of plasma HSP-90α expression 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-90α levels in 120 breast cancer patients(breast cancer group)and 84 patients with benign breast tumors(control group),and the patients were divided into HSP-90α expression-positive and-negative groups using the optimal cut-off value to analyze the relationship between the HSP-90α expression 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-90α was significantly higher in the breast cancer group compared with the control group(P＜0.000 1);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-90α expression level can be used as a good indicator for the diagnosis of malignant breast tumors.The HSP90AA1 gene,which is closely related to the regulation of multiple signaling pathways and is associated with the infiltration of immune cells,may be an important target for the prevention and treatment of breast cancer.
breast cancerplasma HSP-90αHSP90AA1diagnosisprognosis
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