Diagnostic, clinicopathologic, therapeutic and prognostic value of Plasma Heat Shock Protein 90 levels in patients with advanced Gastrointestinal Carcinoma

Abstract

Purpose: Heat shock protein 90 (HSP90) is a critical molecular chaperone for protein folding, intracellular disposition and regulation of tumor biological behavior in the extracellular space. HSP90 has received much attention due to its specific effect in gastrointestinal cancer. This clinical study sought to determine whether HSP90 in plasma may serve as a biomarker in patients with advanced gastrointestinal carcinoma. Methods: Using human plasma samples of advanced gastrointestinal carcinoma, we investigated the specific value of HSP90 in gastrointestinal cancer from a clinical perspective. Results: In summary, plasma levels of HSP90 were shown to be higher in patients with gastric cancer (GC) or colorectal cancer (CRC) than in controls with benign gastrointestinal diseases. In both GC and CRC patients, HSP90 was significantly associated with live metastasis. Higher HSP90 levels were more frequent in CRC patients with hazardous or harmful alcohol consumption habits. Patients with RAS mutations had higher HSP90 levels in CRC. Compared with Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA19-9), HSP90 benefited patients by enhancing diagnostic sensitivity and the Youden index. The levels of HSP90 were inversely associated with short-term efficacy in GC patients who had received fluorouracil/platinum-based advanced first-line treatment. When first-line therapy failed, plasma HSP90 levels in patients with GC were significantly increased. In terms of progression-free survival (PFS), patients with GC or CRC who had low levels of HSP90 were not significantly different from those with high levels of HSP90. Univariate and multivariate analyses demonstrated that HSP90 was not an independent prognostic predictor for GC and CRC patients with PFS. However, RAS mutation was an independent prognostic factor for poor PFS in CRC patients. Conclusions: Plasma HSP90 levels have potential diagnostic value in advanced gastrointestinal carcinoma and therapeutic predictive value in GC.

Plasma Levels of Heat Shock Protein 90 Alpha Associated With Colorectal Cancer Development

“…Previously studies have showed that plasma HSP90α is an excellent biomarker for the diagnosis of lung cancer and liver cancer ( Jhaveri et al, 2014 ; Shi et al, 2014 ; Fu et al, 2017 ). Meanwhile, plasma HSP90α levels were significantly higher than healthy controls in other cancers, but the diagnostic efficiency was insufficient, such as gastric cancer, breast cancer, nasopharyngeal carcinoma and colorectal cancer ( Kasanga et al, 2018 ; Liu et al, 2019 ; Lin et al, 2020 ; Zhang et al, 2020 ). In current study, the plasma HSP90α levels was significantly higher in CRC patients than in healthy controls and consistent with previously reported results ( Kasanga et al, 2018 ).…”

Predictive Value of Serum Heat Shock Protein 90α on the Prognosis of Patients with Lung Adenocarcinoma

“…However, a series of clinical and retrospective analyses have drawn opposing conclusions on the correlation between HSP90α and the prognosis of patients with tumors. For example, Zhang et al 26 found that HSP90α was highly expressed in the peripheral blood of 103 patients with gastric cancer and 83 patients with colorectal cancer, but was not related to the PFS and OS of the patients, whereas in breast cancer, serum HSP90α levels were negatively correlated with OS. 27 , 28 Chen 29 et al compared the expression level of HSP90 in the serum of 137 patients with advanced lung cancer treated with immunotherapy with the PFS and OS of the patients and found that the patients in the high-level group of HSP90α had worse PFS and OS than those in the low-level group.…”

Targeting extracellular Hsp90: A unique frontier against cancer

“…Elevated levels of eHsp90 have been found to correlate with metastatic potential in prostate cancer cell lines ( Hance et al, 2012 ). Plasma Hsp90 has been developed as a biomarker in liver cancer for diagnosis as well as to evaluate efficacy of therapeutic interventions and is also elevated in advanced gastrointestinal malignancies ( Fu et al, 2017 ; Zhang Y. et al, 2020 ; Wei et al, 2020 ). Additionally, plasma levels of Hsp90α are elevated in patients with malignant tumors compared to controls or those with benign tumors and are further elevated in those with metastatic breast cancer compared to localized disease ( Wang et al, 2009 ).…”