Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study
Abstract
:1. Introduction
2. Results
2.1. Patients’ Characteristics
2.2. Gene and Protein Expression
2.3. Patients’ Outcome according to Expression
2.4. Multivariate and Univariate Analysis
3. Discussion
4. Materials and Methods
4.1. Patient’s Population
4.2. Ethics Approval and Consent to Participate
4.3. Immunohistochemistry and Staining Evaluation
4.4. mRNA Expression Analysis
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Feature | Ν | % |
---|---|---|
Selected patients | 171/186 | 91.5 |
Regimen | ||
Carboplatin–paclitaxel | 157 | 91.8 |
Other platinum-based treatment | 14 | 8.2 |
Median age (range) years | 60 (28–84) | |
≤70 years | 145 | 84.8 |
>70 years | 26 | 15.2 |
Histology | ||
Serous | 110 | 64.3 |
Mucinous | 15 | 8.8 |
Endometrioid | 19 | 11.1 |
Clear cell | 7 | 4.1 |
Other epithelial 1 | 20 | 11.7 |
Grade | ||
Well differentiated | 15 | 8.8 |
Moderate | 64 | 37.4 |
Poorly differentiated | 92 | 53.8 |
Stage | ||
I | 26 | 15.2 |
II | 22 | 12.9 |
III | 104 | 60.8 |
IV | 19 | 11.1 |
Surgery | ||
Optimal | 48 | 28.1 |
Others | 121 | 70.8 |
Unknown | 2 | 1.2 |
Second-look laparotomy (SLL) | ||
PCR 2 | 12 | 7.0 |
PPR Micro 3 | 15 | 8.8 |
PPR Macrp 4 | 30 | 17.5 |
Without SLL/unknown | 116 | 66.7 |
Platinum-sensitivity | ||
YES | 79 | 46.2 |
NO | 37 | 21.6 |
Unknown | 55 | 32.2 |
Median survival (range) months | ||
mPFS (95%CI) 5 | 11.4 (95%Cl 9.2–13.5) | |
mOS (95%CI) 6 | 43.1 (95%Cl 34.9–51.4) |
Variables | N | PFS (Months) | p | OS (Months) | p |
---|---|---|---|---|---|
Median (95%CI) | Median (95%CI) | ||||
PKM2 mRNA expression | |||||
Low | 72 | 12.2 (2.4–21.9) | 0.003 | 57.6 (40.0–75.2) | <0.001 |
High | 73 | 7.3 (5.3–9.5) | 30.6 (23.3–37.8) | ||
PKM2 protein expression | |||||
Low | 100 | 14.2 (8.3–20.1) | 0.002 | 53.3 (37.8–68.9) | 0.001 |
High | 71 | 8.7 (6.7–10.7) | 29.3 (26.0–32.6) | ||
CD44 protein expression | |||||
Low | 85 | 13.4 (8.5–18.2) | 0.101 | 50.0 (31.89–68.1) | 0.004 |
High | 86 | 9.2 (7.0–11.4) | 32.6 (26.0–39.2) | ||
PKM2/CD44 proteins’ co-expression | |||||
PKM2Low/CD44 Low | 57 | 16.5 (9.2–23.8) | Ref. | 61.3 (41.6–80.9) | Ref. |
PKM2 High/CD44 High | 51 | 7.4 (4.6–10.1) | 0.0031 | 22.7 (9.4–36.1) | 0.0011 |
PKM2 Low/CD44 High | 38 | 14.2 (1.6–26.8) | 0.7002 | 53.3 (35.6–71.1) | 0.6142 |
PKM2 High/CD44 Low | 25 | 8.5 (5.7–11.2) | 0.0313 | 30.6 (26.5–34.6) | 0.1543 |
PKM2 High/CD44 High | 51 | 7.4 (4.6–10.1) | Ref. | 22.7 (9.4–36.1) | Ref. |
PKM2 Low/CD44 Low | 57 | 16.5 (9.2–23.8) | 0.0034 | 61.3 (41.6–80.9) | 0.0014 |
PKM2 Low/CD44 High | 38 | 14.2 (1.6–26.8) | 0.0225 | 53.3 (35.6–71.1) | 0.0115 |
PKM2 High/CD44 Low | 25 | 8.5 (5.7–11.2) | 0.7496 | 30.6 (26.5–34.6) | 0.1856 |
Variables | Unadjusted Hazard Ratio | 95%CI | p-Value | Adjusted Hazard Ratio | 95%CI | p-Value |
---|---|---|---|---|---|---|
Progression-free survival | ||||||
Age (>70 years versus <70 years) | 1.03 | 0.60–1.60 | 0.896 | - | - | - |
Histology (serous versus others) | 1.13 | 0.76–1.50 | 0.495 | - | - | - |
Grade (poorly versus well-moderate) | 1.73 | 1.21–2.50 | 0.003 | 1.73 | 1.07–2.82 | 0.026 |
Stage (III–IV versus I–II) | 1.67 | 1.08–2.59 | 0.022 | 1.30 | 0.57–2.93 | 0.527 |
Platinum-sensitivity (resistant versus sensitive) | 4.12 | 2.58–6.56 | <0.001 | 3.17 | 1.95–5.14 | <0.001 |
Post-operation residual tumor | 2.15 | 1.39–3.32 | 0.001 | 2.36 | 0.97–5.75 | 0.058 |
PKM2 mRNA | 0.99 | 0.99–1.02 | 0.253 | 0.98 | 0.97–1.003 | 0.984 |
PKM2 mRNA high versus low | 1.74 | 1.20–2.54 | 0.004 | 1.18 | 0.67–2.09 | 0.567 |
PKM2 protein | 1.00 | 1.000–1.004 | 0.043 | 1.002 | 0.999–1.005 | 0.234 |
PKM2 protein high versus low | 1.74 | 1.22–2.48 | 0.002 | 1.95 | 1.23–3.09 | 0.004 |
CD44 protein | 1.01 | 1.002–1.011 | 0.007 | 1.01 | 0.999–1.005 | 0.090 |
CD44 protein high versus low | 1.34 | 0.94–1.90 | 0.102 | 1.21 | 0.77–1.88 | 0.409 |
CD44/PKM2 protein (both high versus others) | 1.69 | 1.16–2.47 | 0.006 | 1.66 | 1.03–2.7 | 0.040 |
OverallSurvival | ||||||
Age (>70years versus <70years) | 1.09 | 0.63–1.89 | 0.770 | - | - | - |
Histology (serous versus others) | 1.45 | 0.97–2.18 | 0.070 | - | - | - |
Grade (poorly versus well-moderate) | 1.45 | 0.97–2.18 | 0.073 | - | - | - |
Stage (III–IV versus I–II) | 1.57 | 0.94–2.62 | 0.084 | - | - | - |
Platinum-sensitivity (resistant versus sensitive) | 4.03 | 2.43–6.68 | <0.001 | 3.11 | 1.85–5.21 | <0.001 |
Post-operation residual tumor | 1.72 | 1.07–2.75 | 0.024 | 3.60 | 1.41–9.21 | 0.008 |
PKM2 mRNA high versus low | 2.15 | 1.39–3.32 | 0.001 | 2.16 | 1.07–4.34 | 0.034 |
PKM2 mRNAscore | 1.00 | 0.99–1.02 | 0.899 | 0.998 | 0.999–1.020 | 0.871 |
PKM2 protein | 1.002 | 1.000–1.005 | 0.050 | 1.003 | 0.999–1.006 | 0.177 |
PKM2 protein high versus low | 1.94 | 1.28–2.94 | 0.002 | 1.82 | 1.05–3.17 | 0.034 |
CD44 protein | 1.006 | 1.006–1.011 | 0.018 | 1.01 | 1.00–1.01 | 0.033 |
CD44 protein (high versus low) | 1.80 | 1.20–2.70 | 0.005 | 1.61 | 0.97–2.68 | 0.065 |
CD44/PKM2 protein (bothhigh versus others) | 2.13 | 1.38–3.30 | 0.001 | 1.99 | 1.10–3.60 | 0.023 |
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Share and Cite
Papadaki, C.; Manolakou, S.; Lagoudaki, E.; Pontikakis, S.; Ierodiakonou, D.; Vogiatzoglou, K.; Messaritakis, I.; Trypaki, M.; Giannikaki, L.; Sfakianaki, M.; et al. Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study. Cancers 2020, 12, 1013. https://doi.org/10.3390/cancers12041013
Papadaki C, Manolakou S, Lagoudaki E, Pontikakis S, Ierodiakonou D, Vogiatzoglou K, Messaritakis I, Trypaki M, Giannikaki L, Sfakianaki M, et al. Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study. Cancers. 2020; 12(4):1013. https://doi.org/10.3390/cancers12041013
Chicago/Turabian StylePapadaki, Chara, Stavroula Manolakou, Eleni Lagoudaki, Spyros Pontikakis, Despo Ierodiakonou, Konstantinos Vogiatzoglou, Ippokratis Messaritakis, Maria Trypaki, Linda Giannikaki, Maria Sfakianaki, and et al. 2020. "Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study" Cancers 12, no. 4: 1013. https://doi.org/10.3390/cancers12041013