Plasma HSP90AA1 Predicts the Risk of Breast Cancer Onset and Distant Metastasis

The purpose of the current study is to develop and validate a comprehensive nomogram containing pre-treatment plasma HSP90AA1 to predict the risk of breast cancer onset and metastasis.

METHODS: We assessed the expression of HSP90s in breast cancer patients using the Online database. To verify the above results, 677 patients diagnosed with breast cancer and 146 patients with benign breast disease between 2014 and 2019 were selected from our hospital divided into cancer risk and metastasis risk cohorts. We focused on HSP90AA1 to elucidate onset and metastasis risks in cohorts.

RESULTS: We found that the expression levels of HSP90AA1, HSP90AA2, HSP90AB1, HSP90B1, and TRAP1 were linked to disease progression. Survival analysis using the GEPIA and OncoLnc databases indicated that the upregulation of HSP90AA1 and HSP90AB1 was related to poor overall survival. In the cancer risk cohort, carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), HSP90AA1, T cells %, natural killer cells %, B cells %, neutrophil count, monocyte count, and d-dimer were incorporated into the nomogram. A high Harrell's concordance index (C-index) value of 0.771(95% CI, 0.725-0.817) could still be reached in the interval validation. In the metastasis risk cohort, predictors contained in the prediction nomogram included the use of CEA, CA153, HSP90AA1, carbohydrate antigen 125(CA125), natural killer cells %, B cells%, platelet count, monocyte count, and d-dimer. C-index was 0.844 (95% CI, 0.801-0.887) and it was well-calibrated. At two cohorts, the intervention threshold is set to 4% and 1%, decision curve analysis shows that nomograms are useful for risk assessment.

CONCLUSIONS: Our study revealed that the appropriate use of pretreatment plasma HSP90AA1 levels in combination with other markers is more effective in predicting breast cancer and metastasis rates.