Heat shock protein 90α (HSP90α) encoded by the HSP90AA1 gene, is the stress inducible isoform of the molecular chaperone HSP90, and was demonstrated as a promising hallmark to diagnose, prognosis in malignant tumors. This study is to evaluate the value of HSP90α in diagnosis, prognosis and immunotherapy of malignant tumors by investigating the expression of HSP90α in plasma of various tumors and analyzing the expression of HSP90α at gene and protein levels via pan-cancer database. We founded that levels of HSP90α in malignant tumors groups were significantly higher than healthy controls in serum. Pan-cancer analysis showed that HSP90AA1 was highly expressed in 27 of 33 tumors, but low in individual cancers (such as renal malignancies). The plasma HSP90α level was positively correlated with the stage of malignant tumor, but there was no significant difference between HSP90AA1 and the stage of most tumors. Cox regression analysis showed that HSP90AA1 expression was significantly correlated with OS in only 6 of the 32 cancers, including LIHC, KIRC, HNSC, LUAD, BRCA and MESO. Up-regulation of HSP90AA1 in most tumors was positively correlated with PDCD1LG2 and CD274 immune checkpoint genes. T cell CD8+ was positively correlated with HSP90AA1 in COAD, DLBC and UVM, and negatively correlated with HSP90AA1 in ESCA, GBM, HNSC, KIRC, KIRP, UCEC and STAD. The AUC of HSP90α are generally high in different tumor groups, which indicated its diagnostic value in malignant tumors. In conclusion, serum HSP90α in patients with malignant tumor is generally elevated, which is of positive significance as an independent diagnosis and combined diagnosis. However, we found that the expression level of HSP90AA1 gene in most tumors was not completely consistent with the serum level, and even down-regulated in some tumors. Plasma levels can be used as biomarkers of poor prognosis in some tumors, but it cannot be used as a biomarker for poor prognosis of all tumors, and more in-depth studies are needed.

Purpose To investigate the expression of heat shock protein 90α (HSP90α) in patients with lung cancer (LC) and the clinical value of HSP90α and other related markers in the diagnosis of LC. Methods Of 335 patients enrolled in the study cohort, 175 were screened for LC and 160 were healthy (HC). The plasma levels of HSP90α and related markers (CEA, NSE, CYFRA21‐1 and ProGRP) were detected in all individuals in the cohort by enzyme‐linked immunosorbent assay (ELISA). Groups were divided according to gender (male/female), age (≤60 years/>60 years), types of LC (small‐cell carcinoma, squamous carcinoma and adenocarcinoma), staging (I, II, III and IV) and metastasis (metastasis and non‐metastasis) separately. Wilcoxon Mann–Whitney test and Kruskal–Wallis test were used to compare statistical differences between two groups/among the multiple groups for each factor of HSP90α. The r ‐value and Kappa were used to compare HSP90α with related markers, and the receiver operating curve (ROC) was used to evaluate the efficacy of plasma HSP90α in predicting LC. Results No statistical difference was found in the plasma level of HSP90α among different age and gender groups ( p > 0.05). In the group divided by LC type, staging and metastasis status, there were statistical differences among different groups in HSP90α level ( p < 0.05). The levels of HSP90α, CEA, NSE, CYFRA21‐1 and ProGRP in LC groups were significantly higher than HC ( p < 0.001). R values of HSP90α correlated with other related markers in the diagnosis of LC ( p < 0.05). Although HSP90α and other related markers did not fit the satisfactory conformance, in terms of the positive rate of diagnosis, it was statistically differences in the diagnostic positive rate between HSP90α and each marker ( p < 0.01). ROC analysis showed that a plasma HSP90α cut‐off point of 50.02 ng/ml had an optimal predictive value for LC. Conclusions HSP90α has significant clinical value in early screening and diagnosis of LC. The combined application of HSP90α and related markers can improve the positive rate of early diagnosis of LC effectively.