Article Data

  • Views 341
  • Dowloads 110

Original Research

Open Access

Clinical diagnostic and prognostic value of plasma Hsp90α in invasive breast cancer

  • Yi Huang1,†
  • Yuanfang Liu2,†
  • Sen Lian3
  • Zhengmin Cai1
  • Yamei Tang1
  • Changyuan Wei4,*,

1Departmentof Research, Guangxi Medical University Cancer Hospital, 530021 Nanning, Guangxi, China

2TCM department, Guangxi Medical University Cancer Hospital, 530021 Nanning, Guangxi, China

3Graduate College of Guangxi Medical University, 530021 Nanning, Guangxi, China

4The Second Departmentof Breast Surgery, Guangxi Medical University Cancer Hospital, 530021 Nanning, Guangxi, China

DOI: 10.22514/ejgo.2022.027 Vol.43,Issue 4,August 2022 pp.58-63

Submitted: 08 June 2022 Accepted: 06 July 2022

Published: 15 August 2022

*Corresponding Author(s): Changyuan Wei E-mail:

† These authors contributed equally.


Invasive breast cancer (IBC) is the most common type of breast cancer. This study aimed to determine whether plasma Hsp90α could be an effective diagnostic and prognostic indicator in IBC patients. The plasma of 545 IBC and 103 non-IBC (NIBC) patients and 189 healthy controls (HC) were collected, and enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma Hsp90α. The accuracy of Hsp90α, carcinoembryonic antigen (CEA), and carbohydrate antigen 153 (CA153) for diagnosing IBC were assessed based on the area under the curve (AUC) of the receiver operating characteristic (ROC) curves. Kaplan-Meier and log-rank tests were employed to analyze the association between plasma Hsp90α levels and progression-free survival (PFS).In the IBC cohort, the plasma levels of Hsp90α were associated with cancer invasion, TNM (Tumor Node Metastasis) stage, and CEA and CA153 levels, and they were remarkably higher in IBC and NIBC than in control. ROC results revealed the AUC values of Hsp90α plasma level in IBC and NIBC were 0.877 (95% CI(Confidence Interval): 0.851–0.900, p < 0.001) and 0.647 (95% CI: 0.589–0.702, p < 0.001). The AUC values of the combination of Hsp90α with CEA and CA153 in IBC and NIBC were 0.903 (95% CI: 0.880–0.924, p < 0.001) and 0.722 (95% CI: 0.667–0.773, p < 0.001). Further, patients with high levels (>81.4 ng/mL) of plasma Hsp90α had a worse PFS than those with low Hsp90α in IBC.Plasma Hsp90α levels could be a reliable diagnostic and prognostic marker in IBC. High plasma Hsp90α levels in IBC was associated with worse PFS.


Heat shock protein 90α; Invasive breast cancer; Diagnostic value; PFS

Cite and Share

Yi Huang,Yuanfang Liu,Sen Lian,Zhengmin Cai,Yamei Tang,Changyuan Wei. Clinical diagnostic and prognostic value of plasma Hsp90α in invasive breast cancer. European Journal of Gynaecological Oncology. 2022. 43(4);58-63.


[1] Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study. JAMA Oncology. 2019; 5: 1749–1768.

[2] Zhang J, Zhao B, Jin F. The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: the analytic results from the SEER database. The Breast Journal. 2019; 25: 838–847.

[3] Sun Y, Zhao Z, Yang Z, Xu F, Lu H, Zhu Z, et al. Risk factors and preventions of breast cancer. International Journal of Biological Sciences. 2017; 13: 1387–1397.

[4] Marrugo-Ramírez J, Mir M, Samitier J. Blood-based cancer biomarkers in liquid biopsy: a promising non-invasive alternative to tissue biopsy. International Journal of Molecular Sciences. 2018; 19: 2877.

[5] Erkeller-Yüksel FM, Isenberg DA, Dhillon VB, Latchman DS, Lydyard PM. Surface expression of heat shock protein 90 by blood mononuclear cells from patients with systemic lupus erythematosus. Journal of Autoimmunity. 1992; 5: 803–814.

[6] Qin L, Huang H, Huang J, Wang G, Huang J, Wu X, et al. Biological characteristics of heat shock protein 90 in human liver cancer cells. American Journal of Translational Research. 2019; 11: 2477–2483.

[7] Liu W, Li J, Zhang P, Hou Q, Feng S, Liu L, et al. A novel pan-cancer biomarker plasma heat shock protein 90alpha and its diagnosis determinants in clinic. Cancer Science. 2019; 110: 2941–2959.

[8] Wei W, Liu M, Ning S, Wei J, Zhong J, Li J, et al. Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma. BMC Cancer. 2020; 20: 6.

[9] Diehl MC, Idowu MO, Kimmelshue K, York TP, Elmore LW, Holt SE. Elevated expression of nuclear Hsp90 in invasive breast tumors. Cancer Biology & Therapy. 2009; 8: 1952–1961.

[10] Simpson NE, Lambert WM, Watkins R, Giashuddin S, Huang SJ, Oxelmark E, et al. High levels of Hsp90 cochaperone p23 promote tumor progression and poor prognosis in breast cancer by increasing lymph node metastases and drug resistance. Cancer Research. 2010; 70: 8446–8456.

[11] Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast cancer-major changes in the American joint committee on cancer eighth edition cancer staging manual. CA: a Cancer Journal for Clinicians. 2017; 67: 290–303.

[12] Song X, Wang X, Zhuo W, Shi H, Feng D, Sun Y, et al. The regulatory mechanism of extracellular Hsp90α on matrix metalloproteinase-2 processing and tumor angiogenesis. The Journal of Biological Chemistry. 2010; 285: 40039–40049.

[13] Wang X, Song X, Zhuo W, Fu Y, Shi H, Liang Y, et al. The regulatory mechanism of Hsp90α secretion and its function in tumor malignancy. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106: 21288–21293.

[14] Lu X, Wang X, Zhuo W, Jia L, Jiang Y, Fu Y, et al. The regulatory mechanism of a client kinase controlling its own release from Hsp90 chaperone machinery through phosphorylation. Biochemical Journal. 2014; 457: 171–183.

[15] Wong DS, Jay DG. Emerging roles of extracellular Hsp90 in cancer. Advances in Cancer Research. 2016; 8: 141–163.

[16] Jego G, Hazoumé A, Seigneuric R, Garrido C. Targeting heat shock proteins in cancer. Cancer Letters. 2013; 332: 275–285.

[17] Jego G, Hermetet F, Girodon F, Garrido C. Chaperoning STAT3/5 by heat shock proteins: interest of their targeting in cancer therapy. Cancers. 2019; 12: 21.

[18] Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nature Reviews Cancer. 2010; 10: 537–549.

[19] Lian M, Zhang C, Zhang D, Chen P, Yang H, Yang Y, et al. The association of five preoperative serum tumor markers and pathological features in patients with breast cancer. Journal of Clinical Laboratory Analysis. 2019; 33: e22875.

[20] Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, et al. High HSP90 expression is associated with decreased survival in breast cancer. Cancer Research. 2007; 67: 2932–2937.

[21] Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature. 2003; 425: 407–410.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time