Chemerin and Chemokine-like Receptor 1 Expression in Ovarian Cancer Associates with Proteins Involved in Estrogen Signaling
Abstract
:1. Introduction
2. Materials and Methods
2.1. Tissue Samples
2.2. Tissue Microarray and Immunohistochemistry
2.3. In Silico Analyses
2.4. Statistical Analysis
3. Results
3.1. Intratumoral RARRES2 mRNA Levels in Ovarian Cancer and Metastasis Tissues Are Significantly Reduced When Compared to Normal Ovary
3.2. Protein Levels of Chemerin and CMKLR1 in Ovarian Cancer Tissue
3.3. Protein Levels of Chemerin and CMKLR1 in Ovarian Cancer Tissue Subject to Levels of Ovarian Cancer Markers, Cancer-Related Proteins and Components of Estrogen Signaling Pathways
3.4. Correlation of Chemerin and CMKLR1 Protein Levels with Intratumoral Expression of Proteins Involved in Estrogen Signaling, Ovarian Cancer Markers, and Other Cancer-Related Genes
3.5. Correlation of RARRES2 and CMKLR1 mRNA Levels with Expression of Genes Involved in Sex Steroid Hormone Metabolism and Signaling Assessed by In Silico Analysis
3.6. Survival Analyses
4. Discussion
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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Characteristics | Number of Patients | (%) |
---|---|---|
208 | 100 | |
FIGO stage | ||
FIGO I | 22 | 10.58 |
FIGO II | 8 | 3.85 |
FIGO III | 65 | 31.25 |
FIGO IV | 50 | 24.04 |
Unknown | 63 | 30.29 |
Histological subtype | ||
Serous | 135 | 64.90 |
Mucinous | 6 | 2.88 |
Endometroid | 10 | 4.81 |
Clear cell | 3 | 1.44 |
Undifferentiated | 54 | 25.96 |
Histological grade | ||
G2 | 53 | 25.48 |
G3 | 122 | 58.65 |
Unknown | 33 | 15.87 |
Marker/Protein | Antibody Clone | Pretreatment | Dilution | Pattern |
---|---|---|---|---|
Chemerin (RARRES2) | LS-B13333 (Biozol) | none | 1:100 | cytoplasmic (non-specific) nuclear |
CMKLR1 | LS-B12924 (Biozol) | none | 1:100 | membranous/cytoplasmic |
ERβ | PPG5/10 (Novus Biologicals) | none | 1:20 | nuclear/cytoplasmic |
ERα | 6F11 (Novocastra) | CC1 64 min | 1:35 | nuclear |
CA-125 | OC125 (Cell Marque) | CC1 52 min | 1:1 | cytoplasmic/membranous |
CEA (polyclonal) | A 0115 (Dako) | P1 8 min | 1:500 | cytoplasmic |
CA72.4 | B72.3 (Alexis Biochemicals) | CC1 36 min | 1:50 | cytoplasmic |
EGFR | E30 (Dako) | P1 4 min | 1:100 | membranous |
p53 | sc-263 (Santa Cruz) | CC1 36 min | 1:2000 | nuclear |
Ki-67 | MIB-1/M7240 (Dako) | CC1 64 min | 1:100 | nuclear |
PR | NCL-L-PGR-312 (Clone 16) (Novocastra) | CC1 64 min | 1:50 | nuclear |
Her2/neu | A0485 (Dako) | CC1 36 min | 1:250 | membranous |
Chemerin | CMKLR1 | Chemerin | CMKLR1 | ||||
---|---|---|---|---|---|---|---|
ERα | low | 1.902 (0.7822) | 2.143 (0.7810) | TP53 | low | 1.910 (0.7926) | 2.090 (0.7781) |
high | 2.049 (0.7400) | 2.195 (0.7490) | high | 1.984 (0.7512) | 2.238 (0.7559) | ||
p = 0.2878 | p = 0.7393 | p = 0.5472 | p = 0.2451 | ||||
ERβ (n) | low | 1.895 (0.7665) | 2.119 (0.7736) | HER2 | low | 1.893 (0.7585) | 2.139 (0.7640) |
high | 2.429 (0.5345) | 2.571(0.5345) | high | 2.133 (0.8193) | 2.200 (0.8052) | ||
p = 0.0683 | p = 0.1372 | p = 0.1355 | p = 0.6702 | ||||
ERβ (cm) | low | 1.838 (0.7423) | 2.060(0.7576) | EGFR | low | 1.905 (0.7739) | 2.119 (0.7757) |
high | 2.212 (0.7809) | 2.424 (0.7513) | high | 2.200 (0.6959) | 2.450 (0.6863) | ||
p = 0.0143 | p = 0.0133 | p = 0.1069 | p = 0.0752 | ||||
PR | low | 1.941 (0.7675) | 2.169 (0.7655) | ERRα | low | 1.671 (0.7082) | 1.753 (0.6827) |
high | 2.231 (0.7250) | 2.308 (0.7511) | high | 2.187 (0.7478) | 2.533 (0.6438) | ||
p = 0.1925 | p = 0.5397 | p < 0.0001 | p < 0.0001 | ||||
CEA | low | 1.908 (0.7889) | 2.107 (0.7671) | ERRβ | low | 1.524 (0.6016) | 1.524 (0.6016) |
high | 2.143 (0.6547) | 2.429 (0.7464) | high | 2.000 (0.7776) | 2.246 (0.7477) | ||
p = 0.1839 | p = 0.0684 | p = 0.0091 | p < 0.0001 | ||||
CA125 | low | 1.950 (0.8256) | 2.000 (0.8584) | ERRγ | low | 1.632 (0.7609) | 1.632 (0.8307) |
high | 1.940 (0.7663) | 2.180 (0.7571) | high | 1.970 (0.7611) | 2.220 (0.7343) | ||
p = 0.9701 | p = 0.3678 | p = 0.0691 | p = 0.0031 | ||||
CA72.4 | low | 1.955 (0.7756) | 2.188 (0.7656) | CMKLR1 | low | 1.314 (0.5827) | |
high | 1.925 (0.7642) | 2.100 (0.7779) | high | 2.127 (0.7226) | |||
p = 0.8374 | p = 0.5349 | p < 0.0001 | |||||
Ki-67 | low | 1.936 (0.7488) | 2.083 (0.7592) | Chemerin | low | 1.560 (0.6440) | |
high | 2.031 (0.8224) | 2.406 (0.7560) | high | 2.447 (0.6527) | |||
p = 0.5490 | p = 0.0304 | p < 0.0001 |
Ovarian Cancer | Serous Ovarian Cancer | |||
---|---|---|---|---|
Chemerin | CMKLR1 | Chemerin | CMKLR1 | |
ERα | n.s. | n.s. | n.s. | n.s. |
PR | p < 0.0001 rho = 0.7952 | n.s. | p < 0.0001 rho = 0.8175 | n.s. |
Ki67 (MKI67) | n.s. | n.s. | n.s. | n.s. |
CA-125 (MUC16) | n.s. | n.s. | n.s. | n.s. |
Her2 | n.s. | n.s. | n.s. | n.s. |
EGFR | n.s. | n.s. | n.s. | n.s. |
p53 | n.s. | n.s. | n.s. | n.s. |
CEA (CEACAM1, 3,4,6,7 and 8) | p = 0.0498 rho = 0.1549 | n.s. | p = 0.0428 rho = 0.1868 | n.s. |
CA72-4 | n.s. | n.s. | n.s. | n.s. |
ERβ (n) | n.s. | p = 0.0009 rho = 0.2641 | p = 0.0213 rho = 0.2127 | p = 0.0039 rho = 0.2630 |
ERβ (cm) | p = 0.0137 rho = 0.2009 | p = 0.007 rho = 0.216 | p = 0.0029 rho = 0.2731 | p = 0.003 rho = 0.2700 |
ERRα | p < 0.0001 rho = 0.384 | p < 0.0001 rho = 0.5207 | p < 0.0001 rho = 0.3989 | p < 0.0001 rho = 0.4709 |
ERRβ | p < 0.0001 rho = 0.3343 | p < 0.0001 rho = 0.4239 | p = 0.0007 rho = 0.3082 | p < 0.0001 rho = 0.3665 |
ERRγ | p < 0.0001 rho = 0.3830 | p < 0.0001 rho = 0.4198 | p < 0.0001 rho = 0.4534 | p < 0.0001 rho = 0.4869 |
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Weber, F.; Schueler-Toprak, S.; Buechler, C.; Ortmann, O.; Treeck, O. Chemerin and Chemokine-like Receptor 1 Expression in Ovarian Cancer Associates with Proteins Involved in Estrogen Signaling. Diagnostics 2023, 13, 944. https://doi.org/10.3390/diagnostics13050944
Weber F, Schueler-Toprak S, Buechler C, Ortmann O, Treeck O. Chemerin and Chemokine-like Receptor 1 Expression in Ovarian Cancer Associates with Proteins Involved in Estrogen Signaling. Diagnostics. 2023; 13(5):944. https://doi.org/10.3390/diagnostics13050944
Chicago/Turabian StyleWeber, Florian, Susanne Schueler-Toprak, Christa Buechler, Olaf Ortmann, and Oliver Treeck. 2023. "Chemerin and Chemokine-like Receptor 1 Expression in Ovarian Cancer Associates with Proteins Involved in Estrogen Signaling" Diagnostics 13, no. 5: 944. https://doi.org/10.3390/diagnostics13050944