High mRNA Expression Levels of Heat Shock Protein Family B Member 2 (HSPB2) Are Associated with Breast Cancer Patients’ Relapse and Poor Survival
Abstract
:1. Introduction
2. Results
2.1. Downregulation of HSPB2 Gene Expression Levels during Oncogenic Transformation in Mammary Epithelial Cells
2.2. Clinicopathological and Biological Characteristics of BrCa Patients and Used Samples
2.3. Reduced Expression Levels of HSPB2 mRNA in Breast Carcinoma Tissues as Compared with Paired Non-Cancerous Tissues
2.4. HSPB2 mRNA Overexpression Is a Reliable Predictor of Poor Prognosis in BrCa Patients, Independent of Other Clinicopathological Factors
2.5. Prognostic Value of HSPB2 mRNA Expression in Patients with Breast Adenocarcinoma, Stratified According to Molecular Subtype, Anatomic Stage, or Prognostic Stage
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Cell Culture Conditions
4.2. Patients and Tissue Collection
4.3. Total RNA Extraction and First-Strand cDNA Synthesis
4.4. Quantitative Real-Time PCR (qPCR)
4.5. Biostatistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number of Patients (%) | |
---|---|
Patients | 150 |
HSPB2 mRNA Expression Status | |
Negative | 75 (50.0%) |
Positive | 75 (50.0%) |
Age (y) | Median: 60; Range: 31–90 |
Tumor Size (cm2) | Median: 2.35; Range: (0.60–8.50) |
Cancer Type | |
Invasive ductal carcinoma | 121 (80.7%) |
Lobular carcinoma | 16 (10.7%) |
Other carcinomas | 13 (8.6%) |
Molecular Subtype | |
Luminal A | 59 (39.3%) |
Luminal B | 40 (26.7%) |
Triple-negative | 36 (24.0%) |
HER2-enriched | 15 (10.0%) |
Histological Grade | |
I | 8 (5.3%) |
II | 97 (64.7%) |
III | 45 (30.0%) |
HER2 Status | |
Negative | 115 (79.3%) |
Positive | 30 (20.7%) |
Unknown | 5 |
ER Status | |
Negative | 56 (37.3%) |
Positive | 94 (62.7%) |
PR Status | |
Negative | 82 (54.7%) |
Positive | 68 (45.3%) |
Ki-67 Index | |
Low (≤14%) | 92 (63.9%) |
High (>14%) | 52 (36.1%) |
Unknown | 6 |
Anatomic Stage | |
I | 43 (28.7%) |
II | 89 (59.3%) |
III | 18 (12.0%) |
Prognostic Stage | |
I | 60 (40.0%) |
II | 68 (45.3%) |
III | 22 (14.7%) |
Variable | Mean ± SE | Range | Percentiles | ||
---|---|---|---|---|---|
25th | 50th (Median) | 75th | |||
HSPB2 mRNA Expression (RQU) | |||||
in breast cancer tissues (n = 150) | 2215.7 ± 265.8 | 29.0–19,101.0 | 315.5 | 656.5 | 2637.8 |
in non-cancerous tissues (n = 16) | 11,234.5 ± 3094.54 | 340.0–40,093.0 | 1864.0 | 5778.5 | 15,170.3 |
Univariate Analysis (n = 145) | Multivariable Analysis 1 (n = 145) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Covariate | HR 2 | 95% CI 3 | p Value 4 | BCa Bootstrap 95% CI 3 | Bootstrap p Value 4 | HR 2 | 95% CI 3 | p Value 4 | BCa Bootstrap 95% CI 3 | Bootstrap p Value 4 |
HSPB2 mRNA expression status | ||||||||||
Negative (n = 71) | 1.00 | 1.00 | ||||||||
Positive (n = 74) | 2.29 | 1.19–4.42 | 0.014 | 1.17–4.82 | 0.014 | 2.61 | 1.34–5.08 | 0.005 | 1.26–6.61 | 0.006 |
Molecular subtype | <0.001 | 0.071 | ||||||||
Luminal A (n = 56) | 1.00 | 1.00 | ||||||||
Luminal B (n = 39) | 1.02 | 0.36–2.88 | 0.97 | 0.31–3.11 | 0.97 | 1.27 | 0.45–3.60 | 0.65 | 0.24–4.65 | 0.66 |
Triple-negative (n = 35) | 3.63 | 1.60–8.21 | 0.002 | 1.45–10.88 | 0.003 | 2.04 | 0.83–5.02 | 0.12 | 0.78–7.18 | 0.094 |
HER2-enriched (n = 15) | 6.04 | 2.44–14.96 | <0.001 | 2.40–19.65 | <0.001 | 3.59 | 1.35–9.20 | 0.010 | 1.42–11.78 | 0.005 |
Prognostic stage | <0.001 | 0.013 | ||||||||
I (n = 58) | 1.00 | 1.00 | ||||||||
II (n = 66) | 5.00 | 1.90–13.10 | 0.001 | 1.78–4.89 × 104 | 0.002 | 3.72 | 1.33–10.38 | 0.012 | 0.99–1.10 × 105 | 0.010 |
III (n = 21) | 10.06 | 3.53–28.63 | <0.001 | 2.87–87.66 | <0.001 | 6.22 | 1.83–21.12 | 0.003 | 1.4–1.45 × 106 | 0.005 |
Univariate Analysis (n = 145) | Multivariable Analysis 1 (n = 145) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Covariate | HR 2 | 95% CI 3 | p Value 4 | BCa Bootstrap 95% CI 3 | Bootstrap p Value 4 | HR 2 | 95% CI 3 | p Value 4 | BCa Bootstrap 95% CI 3 | Bootstrap p Value 4 |
HSPB2 mRNA expression status | ||||||||||
Negative (n = 71) | 1.00 | 1.00 | ||||||||
Positive (n = 74) | 2.45 | 1.23–4.96 | 0.011 | 1.21–5.79 | 0.015 | 2.69 | 1.33–5.42 | 0.006 | 1.23–7.98 | 0.007 |
Molecular subtype | <0.001 | 0.085 | ||||||||
Luminal A (n = 56) | 1.00 | 1.00 | ||||||||
Luminal B (n = 39) | 1.16 | 0.40–3.35 | 0.78 | 3.66–38.89 | 0.79 | 1.27 | 0.44–3.66 | 0.66 | 0.30–4.40 | 0.67 |
Triple-negative (n = 35) | 4.66 | 2.04–10.66 | <0.001 | 15.17–3.89 × 106 | <0.001 | 3.22 | 1.26–8.23 | 0.014 | 1.26–10.23 | 0.008 |
HER2-enriched (n = 15) | 3.54 | 1.23–10.22 | 0.019 | 12.50–2.69 × 105 | 0.011 | 2.45 | 0.79–7.59 | 0.12 | 0.47–10.17 | 0.14 |
Prognostic stage | 0.16 | |||||||||
I (n = 58) | 1.00 | 1.00 | ||||||||
II (n = 66) | 2.26 | 0.99–5.16 | 0.053 | 0.96–6.20 | 0.046 | 1.62 | 0.67–3.92 | 0.29 | 0.64–4.88 | 0.23 |
III (n = 21) | 6.00 | 2.44–14.71 | <0.001 | 2.29–17.55 | <0.001 | 2.86 | 0.96–8.53 | 0.059 | 0.82–15.54 | 0.049 |
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Sklirou, A.D.; Gianniou, D.D.; Karousi, P.; Cheimonidi, C.; Papachristopoulou, G.; Kontos, C.K.; Scorilas, A.; Trougakos, I.P. High mRNA Expression Levels of Heat Shock Protein Family B Member 2 (HSPB2) Are Associated with Breast Cancer Patients’ Relapse and Poor Survival. Int. J. Mol. Sci. 2022, 23, 9758. https://doi.org/10.3390/ijms23179758
Sklirou AD, Gianniou DD, Karousi P, Cheimonidi C, Papachristopoulou G, Kontos CK, Scorilas A, Trougakos IP. High mRNA Expression Levels of Heat Shock Protein Family B Member 2 (HSPB2) Are Associated with Breast Cancer Patients’ Relapse and Poor Survival. International Journal of Molecular Sciences. 2022; 23(17):9758. https://doi.org/10.3390/ijms23179758
Chicago/Turabian StyleSklirou, Aimilia D., Despoina D. Gianniou, Paraskevi Karousi, Christina Cheimonidi, Georgia Papachristopoulou, Christos K. Kontos, Andreas Scorilas, and Ioannis P. Trougakos. 2022. "High mRNA Expression Levels of Heat Shock Protein Family B Member 2 (HSPB2) Are Associated with Breast Cancer Patients’ Relapse and Poor Survival" International Journal of Molecular Sciences 23, no. 17: 9758. https://doi.org/10.3390/ijms23179758