Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer
Abstract
:1. Introduction
2. Results
2.1. H3K9ac Staining in Cervical Carcinoma
2.2. H3K4me3 Staining in Cervical Cancer
2.3. Correlation Analysis between H3K4me3 and p16 Oncoprotein
2.4. Role of H3K9ac and H3K4me3 for Overall Survival
2.5. Role of H3K9ac and H3K4me3 for Progress-Free Survival
2.6. Cox Regression of H3K9ac and H3K4me3 and Clinic Pathological Variables
3. Discussion
4. Materials and Methods
4.1. Patients and Specimens
4.2. Ethics Approval
4.3. Immunohistochemistry
4.4. Statistics
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
H3K9ac | histone H3 acetyl K9 |
H3K4me3 | histone H3 tri methyl K4 |
SCC | squamous cell carcinoma |
References
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Item | No./Total No. | % |
---|---|---|
Age, years | ||
<49 | 139/250 | 55.6 |
>49 | 111/250 | 44.4 |
Number of Positive Nodes | ||
0 | 151/250 | 60.4 |
≥1 | 97/250 | 38.8 |
Not available (NA’s) | 2/250 | 0.8 |
Tumor Size, pT | ||
pT1 | 110250 | 44 |
pT2/3/4 | 137/250 | 54.8 |
Not available (NA’s) | 3/250 | 1.2 |
FIGO | ||
I | 64/250 | 25.6 |
II/III/IV | 92/250 | 36.8 |
Not available (NA’s) | 94/250 | 37.6 |
Tumor Grade | ||
I | 21/250 | 8.4 |
II | 143/250 | 57.2 |
III | 78/250 | 31.2 |
Not available (NA’s) | 8/250 | 3.2 |
Tumor Subtype | ||
Squamous | 202/250 | 80.8 |
Adenocarcinoma | 48/250 | 19.2 |
Progression (over 235 months) | ||
None | 210/250 | 84 |
At least one | 21/250 | 11.6 |
Not available (NA’s) | 11/250 | 4.4 |
Survival (over 235 months) | ||
Right censured | 190/250 | 76 |
Died | 49/250 | 19.6 |
Not available (NA’s) | 11/250 | 4.4 |
H3K9ac | H3K4me3 (Cytoplasmic) | H3K4me3 (Nuclear) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Median IRS (+/−SD) | % | p (NPAR) | ρ | Median IRS (+/−SD) | % | p (NPAR) | ρ | Median IRS (+/−SD) | % | p (NPAR) | ρ | |
Histology | ||||||||||||
SCC | 4 (+/−3.45) | 40.10% | 0.013 | - | 0 (+/−2.67) | 57.40% | 0.296 | - | 8 (+/−3.56) | 32.20% | 0.603 | - |
Adeno-Ca | 8 (+/−3.78) | 31.30% | 0 (+/−3.35) | 52.10% | 8 (+/−3.58) | 27.10% | ||||||
Grade | ||||||||||||
G1 | 8 (+/−3.51) | 31.00% | 0.004 | −0.209 (p = 0.001) | 0 (+/−2.94) | 57.10% | 0.197 | 0.082 (p > 0.05) | 8 (+/−3.66) | 28.60% | 0.917 | −0.017 (p > 0.05) |
G2 | 4 (+/−3.57) | 35.00% | 0 (+/−3.08) | 52.40% | 8 (+/−3.59) | 31.50% | ||||||
G3 | 4 (+/−3.26) | 41.00% | 0 (+/−2.24) | 62.80% | 8 (+/−3.55) | 33.30% | ||||||
pN | ||||||||||||
N− | 4 (+/−3.55) | 86.10% | 0.001 | −0.236 (p = 0.000) | 0 (+/−3.02) | 57.00% | 0.981 | −0.001 (p > 0.05) | 8 (+/−3.50) | 32.50% | 0.695 | 0.025 (p > 0.05) |
N+ | 4 (+/−3.33) | 66.00% | 0 (+/−2.43) | 55.70% | 8 (+/−3.69) | 28.90% | ||||||
pT | ||||||||||||
T1 | 4 (+/−3.52) | 30.90% | 0.035 | −0.149 (p = 0.019) | 0 (+/−2.34) | 69.10% | 0.002 | 0.191 (p = 0.003) | 8 (+/−3.49) | 30.00% | 0.171 | 0.081 (p > 0.05) |
T2/3/4 | 4 (+/−3.49) | 40.90% | 2 (+/−2.93) | 3.60% | 8 (+/−3.60) | 32.10% | ||||||
FIGO | ||||||||||||
I | 8 (+/−3.91) | 26.60% | 0.016 | −0.192 (p = 0.016) | 0 (+/−2.45) | 64.10% | 0.324 | 0.070 (p = 0.384) | 8 (+/−3.37) | 32.80% | 0.862 | −0.005 (p = 0.948) |
II+ | 4 (+/−3.44) | 23.90% | 2 (+/−2.66) | 5.40% | 8 (+/−3.67) | 30.40% | ||||||
p16 | - | - | - | 0.047 (p > 0.05) | - | - | - | 0.009 (p > 0.05) | - | - | - | 0.144 (p = 0.027) |
Variable | Significance | Hazard Ratio of Exp(B) | Lower 95% CI of Exp(B) | Upper 95% CI of Exp(B) |
---|---|---|---|---|
Histology | 0.040 | 1.893 | 1.030 | 3.479 |
pT | 0.751 | 0.910 | 0.509 | 1.626 |
pN | 0.003 | 2.447 | 1.367 | 4.380 |
FIGO | 0.012 | 3.181 | 1.287 | 7.863 |
Grading | 0.198 | 1.360 | 0.852 | 2.170 |
Age at surgery | 0.000 | 1.049 | 1.026 | 1.072 |
H3K9ac | 0.027 | 1.900 | 1.076 | 3.356 |
H3K4me3 nucleus | 0.708 | 1.216 | 0.436 | 3.389 |
H3K4me3 cytoplasm | 0.159 | 1.503 | 0.853 | 2.651 |
Variable | Significance | Hazard Ratio of Exp(B) | Lower 95% CI of Exp(B) | Upper 95% CI of Exp(B) |
---|---|---|---|---|
Histology | 0.753 | 1.156 | 0.469 | 2.851 |
pT | 0.760 | 0.890 | 0.423 | 1.875 |
pN | 0.843 | 1.082 | 0.495 | 2.368 |
FIGO | 0.044 | 3.085 | 1.031 | 9.235 |
Grading | 0.521 | 1.228 | 0.656 | 2.299 |
Age at surgery | 0.157 | 1.021 | 0.992 | 1.052 |
H3K9ac | 0.763 | 0.890 | 0.417 | 1.900 |
H3K4me3 nucleus | 0.476 | 0.681 | 0.236 | 1.963 |
H3K4me3 cytoplasm | 0.030 | 2.278 | 1.084 | 4.790 |
Histone H3 Acetyl K9 1 | Histone H3 Tri Methyl K4 2 |
---|---|
Blocking solution 3: 5 min | Blocking solution 3: 5 min |
primary antibody 1: 1:200 in PBS 5, incubation: 16 h, 4 °C | primary antibody 2: 1:500 in PBS 5, incubation: 16 h, 4 °C |
PostBlock 3: 20 min | PostBlock 3: 20 min |
HRP Polymer 3: 30 min | HRP Polymer 3: 30 min |
Chromogen: DAB 4 (0.5 min) | Chromogen: DAB 4 (1 min) |
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Beyer, S.; Zhu, J.; Mayr, D.; Kuhn, C.; Schulze, S.; Hofmann, S.; Dannecker, C.; Jeschke, U.; Kost, B.P. Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer. Int. J. Mol. Sci. 2017, 18, 477. https://doi.org/10.3390/ijms18030477
Beyer S, Zhu J, Mayr D, Kuhn C, Schulze S, Hofmann S, Dannecker C, Jeschke U, Kost BP. Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer. International Journal of Molecular Sciences. 2017; 18(3):477. https://doi.org/10.3390/ijms18030477
Chicago/Turabian StyleBeyer, Susanne, Junyan Zhu, Doris Mayr, Christina Kuhn, Sandra Schulze, Simone Hofmann, Christian Dannecker, Udo Jeschke, and Bernd P. Kost. 2017. "Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer" International Journal of Molecular Sciences 18, no. 3: 477. https://doi.org/10.3390/ijms18030477
APA StyleBeyer, S., Zhu, J., Mayr, D., Kuhn, C., Schulze, S., Hofmann, S., Dannecker, C., Jeschke, U., & Kost, B. P. (2017). Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer. International Journal of Molecular Sciences, 18(3), 477. https://doi.org/10.3390/ijms18030477