High HSP60 Expression Signals Poor Prognosis, Aggressive Tumors in Ovarian Cancer

High heat shock protein 60 (HSP60) expression in patients with ovarian cancer is associated with poor prognosis and aggressive tumor characteristics, according to a study published in the International Journal of General Medicine.¹

HSPs are highly conserved molecular chaperones that maintain cellular homeostasis under stressful conditions, like heat shock or toxin exposure. In particular, HSP60 is critical in mitochondrial function, protein folding, and cellular survival. Past studies found that HSP60 is overexpressed in several cancers, like breast, colorectal, and lung cancers, where it is associated with tumor progression, resistance to apoptosis, and metastasis.

Similarly, a previous study found that HSP60 expression is upregulated in ovarian cancer.² However, its role as a prognostic biomarker and the mechanisms by which it contributes to ovarian cancer’s aggressive behavior and treatment resistance remain underexplored.¹

Consequently, the researchers investigated the clinical significance of HSP60 expression in patients with ovarian cancer by analyzing its association with clinicopathological features, overall survival (OS), and disease-free survival (DFS). They also explored how their findings could translate into clinical practice, like developing targeted therapies, enabling risk stratification, or tailoring patient management strategies based on HSP60 expression levels.

High heat shock protein 60 (HSP60) expression is associated with larger tumors, advanced stages, and worse survival outcomes, highlighting its potential as a prognostic ovarian cancer biomarker. | Image Credit: MohammedElAmine - stock.adobe.com

To do so, the researchers enrolled 260 patients diagnosed with ovarian cancer between January 2017 and December 2019 at The First Affiliated Hospital of Chengdu Medical College in China. All patients received treatment based on the National Comprehensive Cancer Network (NCCN) guidelines post-enrollment, with the follow-up period concluding in December 2023. They also enrolled 260 control patients with normal ovarian tissues who underwent total hysterectomy and bilateral adnexectomy due to uterine myomas.

Within both cohorts, they analyzed DFS and OS. DFS was considered the time from cytoreductive surgery to recurrence or death from any cause. Similarly, OS was measured from the date of cytoreductive surgery until either death or the last follow-up. The researchers used Kaplan-Meier survival curves to compare survival differences, while they evaluated prognostic factors through multivariable analysis using the Cox proportional hazards regression model.

Additionally, HSP60 expression was evaluated using immunohistochemistry staining on full tumor slides; two independent pathologists randomly reviewed them on 2 separate occasions. Staining intensity was graded on a 4-point scale, with 0 indicating no staining, 1 for weak, 2 for moderate, and 3 for strong intensity. Also, the researchers scored the proportion of positively stained cells with 0 for no stained cells, 1 for 1% to 25%, 2 for 26% to 50%, 3 for 51% to 75%, and 4 for greater than 75%.

Each patient’s final score was calculated by multiplying the intensity score by the percentage score, using the score of 8 as a cut-off point. Therefore, tumors with scores below 8 were considered to have low HSP60 expression and those with scores of 8 or higher were classified as having high HSP60 expression.

Through the immunohistochemical analysis, the researchers determined that 91.54% (n = 238) of the cancerous tissues showed HSP60 staining compared with 11.15% (n = 29) of the normal tissues; this difference was statistically significant (P < .0001).

They noted that high HSP60 expression was significantly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P = .0001), lymph node metastasis (P = .0005), and tumor size (P = .0001). Therefore, patients with high HSP60 expression exhibited larger tumors, more advanced FIGO stages, and increased lymph node involvement.

Additionally, the Kaplan-Meier analysis found that patients with high HSP60 expression experienced significantly poorer OS than those with low HSP60 expression (P = .004). The univariate analysis identified age, tumor differentiation, FIGO stage, lymph node metastasis, and HSP60 expression status as risk factors influencing OS. After adjusting for confounders, the multivariate analysis identified lymph node metastasis (P = .002), FIGO stage (P = .002), and HSP60 expression status (P = .003) as independent risk factors for OS.

As for DFS, the Kaplan-Meier analysis showed that patients with high HSP60 expression had notably shorter DFS than those with low HSP60 expression (P = .002). Also, the univariate analysis found that tumor size, lymph node metastasis, tumor differentiation, FIGO stage, and HSP60 expression influenced DFS. After adjusting for potential confounding variables, the multivariate analysis determined that lymph node metastasis (P = .005), FIGO stage (P = .001), and HSP60 expression (P = .001) were independent DFS risk factors.

The researchers acknowledged their study’s limitations, including that it was conducted within a relatively homogenous population from a single health care center. This could potentially restrict the generalizability of their findings. However, they expressed confidence in their findings and suggested areas for further research.

“The strong association between high HSP60 expression and poor survival outcomes highlights the need for further research into the mechanisms by which HSP60 promotes tumor progression,” the authors concluded. “…Future studies should focus on validating these findings in larger cohorts and exploring the feasibility of incorporating HSP60-targeted therapies into the clinical management of ovarian cancer.”

References

1. Zheng M, Li S, Deng J, Huang C, Zhang H. Identification and Clinical Validation of High HSP60 Expression Predicts Poor Prognosis in Patients with Ovarian Cancer. Int J Gen Med. 2025;18:103-111. doi:10.2147/IJGM.S499524
2. 2.Guo J, Li X, Zhang W, et al. HSP60-regulated mitochondrial proteostasis and protein translation promote tumor growth of ovarian cancer. Scientific Reports. 2019;9(1). doi:10.1038/s41598-019-48992-7