Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis
Abstract
:1. Introduction
2. Results
2.1. Immunohistochemical Expression of COX-2
2.2. PGE2 Composition and PTGS1, PTGS2, PTGES3, TERT Expression in CRC
2.3. Isoform Gene Expression Analysis
2.4. Multi-Omics Analysis
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Prostaglandin E2 Expression
4.3. Immunohistochemistry (IHC)
4.4. Telomeric Repeat Amplification Protocol (TRAP)
4.5. TCGA Data Extraction and RNA-Seq Analysis
4.6. Isoform Analysis
4.7. Survival Analysis
4.8. Data Extraction from the Human Protein Atlas (HPA) and Protein Expression Analysis
4.9. Statistical Analysis
4.10. Multi-Omics Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Percentage (%) of Positive COX-2 Immunostaining by IHC | COX-2 Staining Intensity by IHC | |||||
---|---|---|---|---|---|---|
CRC Patient ID# | Low (≤25% of Epithelial Cancer Cells) | Medium (>25% & ≤50% of Epithelial Cancer Cells) | High (>50% of Epithelial Cancer Cells) | Weak | Moderate | Strong |
1405E/03 | + | + | ||||
2571D/03 | + | + | ||||
1044G/03 | + | + | ||||
2906E/04 | + | + | ||||
2908D/04 | + | + | ||||
3661E/03 | + | + | ||||
1404E/03 | + | + | ||||
856E/03 | + | + | ||||
2909D/04 | + | + | ||||
2831D/04 | + | + | ||||
975D/02 | Negative staining | |||||
2904Z/04 | + | + | ||||
948G/03 | + | + | ||||
348E/03 | + | + | ||||
5071D/03 | + | + | ||||
988E/04 | + | + | ||||
6003G/02 | + | + | ||||
977E/03 | + | + | ||||
857E/03 | Negative staining | |||||
304D/03 | + | + | ||||
3986E | + | + | ||||
1694G/03 | + | + | ||||
1096 | + | + | + | |||
1254G | Negative staining | |||||
5433G | + | + | + | |||
633Z | + | + | ||||
987E/04 | + | + | ||||
423D/03 | + | + | ||||
656D/03 | + | + | ||||
4961D/02 | + | + | ||||
5025E/02 | + | + | ||||
482E/03 | + | + | ||||
770E/03 | + | + | ||||
3386E | + | + | ||||
1403D/03 | + | + | ||||
5758G/02 | + | + | ||||
5565G | + | + | ||||
635D | + | + | ||||
3701D | + | + | ||||
3876D | + | + | ||||
8122/03 | Negative staining | |||||
4975E/02 | Negative staining | |||||
5024Z | + | + | ||||
5013D | + | + | ||||
5163Z/02 | Negative staining | |||||
5884E/02 | + | + | ||||
5024Z/02 | Negative staining | |||||
5019D/03 | Negative staining | |||||
5199G/02 | Negative staining |
Variable | Normal Mucosa | Cancer Tissue | ||||||
---|---|---|---|---|---|---|---|---|
No | Mean | SD | p-Value | No | Mean | SD | p-Value | |
All cases | 35 | 2374.04 | 1695.081 | 34 | 1589.622 | 1075.305 | 0.013 | |
Sex | ||||||||
Male | 13 | 1976.704 | 1477.7668 | 13 | 2034.405 | 1305.7355 | ||
Female | 22 | 2866.836 | 2109.3560 | 0.056 | 21 | 1314.280 | 822.6191 | 0.191 |
Smoke | ||||||||
No | 24 | 2374.842 | 1669.7945 | 24 | 1419.926 | 860.0917 | ||
Yes | 8 | 2796.588 | 2498.2338 | 0.59 | 7 | 1667.929 | 1206.1716 | 0.545 |
BMI | ||||||||
<25 | 19 | 2244.542 | 1745.6862 | 19 | 1812.677 | 1191.0385 | ||
≥25 | 16 | 2882.578 | 2124.8944 | 0.336 | 15 | 1307.085 | 865.2102 | 0.177 |
Duke’s stage | ||||||||
A | 0 | 0 | ||||||
B | 16 | 3273.561 | 2036.8244 | 15 | 1696.322 | 904.9637 | ||
C | 15 | 1930.935 | 1782.8859 | 15 | 1423.153 | 1294.7909 | ||
D | 4 | 1856.634 | 1055.7880 | 4 | 1813.756 | 900.6809 | ||
A+B | 16 | 3273.561 | 2036.8244 | 0.036 | 15 | 1696.322 | 904.9637 | 0.615 |
C+D | 19 | 1915.293 | 1630.6619 | 19 | 1505.385 | 1210.7447 | ||
Grade | ||||||||
low | 4 | 2617.679 | 1318.3896 | 4 | 1261.628 | 802.6919 | ||
moderate | 28 | 2682.486 | 2039.2589 | 27 | 1700.093 | 1127.0442 | ||
high | 3 | 1062.409 | 859.9787 | 0.393 | 3 | 1032.711 | 868.3637 | 0.495 |
Tumor site | ||||||||
Right | 7 | 1667.951 | 1410.0214 | 7 | 936.412 | 523.005 | ||
Left | 7 | 2929.321 | 2674.6937 | 7 | 2077.241 | 1396.8070 | ||
Sigmoid | 10 | 2580.901 | 1377.0804 | 10 | 1536.713 | 1007.5961 | ||
Rectum | 11 | 2797.966 | 2169.4357 | 0.236 | 10 | 1758.445 | 1090.7798 | 0.608 |
Right colon | 7 | 1667.951 | 1410.0214 | 7 | 936.412 | 523.0055 | ||
Left colon | 28 | 2753.282 | 1996.2152 | 0.186 | 27 | 1758.973 | 1122.4103 | 0.071 |
Colon | 24 | 2416.246 | 1841.0003 | 24 | 1519.279 | 1084.3813 | ||
Rectum | 11 | 2797.966 | 2169.4357 | 0.594 | 10 | 1758.445 | 1090.7798 | 0.563 |
Ki-67 expression | ||||||||
negative | 3 | 3617.660 | 2180.4306 | 3 | 1245.514 | 643.9262 | ||
positive | 32 | 2434.830 | 1907.2952 | 0.449 | 31 | 1622.923 | 1109.6303 | 0.441 |
p53 expression | ||||||||
negative | 12 | 3271.839 | 1679.5463 | 12 | 1526.599 | 861.8398 | ||
positive | 23 | 2152.412 | 1967.9908 | 0.09 | 22 | 1623.998 | 1193.4976 | 0.786 |
Characteristic | No. |
---|---|
Patients | |
Cancer tissue | 49 |
Adjacent normal tissues | 49 |
Sex | |
Male | 28 |
Female | 21 |
Smoking | |
Yes | 12 |
No | 34 |
BMI | |
<25 | 21 |
≥25 | 25 |
Dukes staging system | |
B | 25 |
C | 19 |
D | 5 |
Histology grade | |
High | 4 |
Medium | 41 |
Low | 4 |
Tumor location | |
Right colon | 8 |
Left colon | 24 |
Rectum | 17 |
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Share and Cite
Ayiomamitis, G.D.; Notas, G.; Vasilakaki, T.; Tsavari, A.; Vederaki, S.; Theodosopoulos, T.; Kouroumalis, E.; Zaravinos, A. Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis. Cancers 2019, 11, 1536. https://doi.org/10.3390/cancers11101536
Ayiomamitis GD, Notas G, Vasilakaki T, Tsavari A, Vederaki S, Theodosopoulos T, Kouroumalis E, Zaravinos A. Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis. Cancers. 2019; 11(10):1536. https://doi.org/10.3390/cancers11101536
Chicago/Turabian StyleAyiomamitis, Georgios D., George Notas, Thivi Vasilakaki, Aikaterini Tsavari, Styliani Vederaki, Theodosis Theodosopoulos, Elias Kouroumalis, and Apostolos Zaravinos. 2019. "Understanding the Interplay between COX-2 and hTERT in Colorectal Cancer Using a Multi-Omics Analysis" Cancers 11, no. 10: 1536. https://doi.org/10.3390/cancers11101536