Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients’ Selection
2.2. LARC Diagnosis
2.3. Treatment of LARC
2.4. Evaluation of Tumor Response to TNT
2.5. SEPT9m Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CRC | Colorectal cancer |
RC | Rectal cancer |
LARC | Locally advanced rectal cancer |
cCR | Complete clinical response |
TNT | Total neoadjuvant therapy |
WW | Watch and wait |
SEPT9m | SEPTIN9 gene methylation |
SEPT9mr | SEPTIN9 gene methylation ratio |
DRE | Digital rectal examination |
MRI | Magnetic resonance imaging |
mTRG | MRI Tumor Regression Grade |
cfDNA | Cell-free DNA |
ddPCR | Droplet digital polymerase chain reaction |
cTR | Complete tumor response |
cPR | Complete pathological response |
CEA | Carcinoembryonic antigen |
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Age (Years) | 63.3 (38–80) |
Sex | |
Male | 24 (61.5%) |
Female | 15 (38.5%) |
Tumor size (cm) | 4.3 (2–8.5) |
T stage | |
T1 | 0 (0%) |
T2 | 2 (5.1%) |
T3 | 31 (79.5%) |
T4 | 6 (15.4%) |
N stage | |
N0 | 4 (10.3%) |
N1 | 20 (51.3%) |
N2 | 15 (38.5%) |
SEPT9mr | 0.0317 (0.008–0.125) |
cTR | cCR | 23 (59%) | |
Non-cCR but cPR | 4 (10.3%) | 27 (69.2%) | |
Non-cTR | Non-cCR nor cPR | 12 (30.8%) | 12 (30.8%) |
cTR | p | OR (95% CI) | ||
---|---|---|---|---|
No | Yes | |||
Age (years) | 62.0 ± 12.2 | 63.9 ± 10.5 | 0.624 | 1.02 (0.95, 1.08) |
Sex | 0.580 | |||
Male | 6 (50.0%) | 18 (66.7%) | ||
Female | 6 (50.0%) | 9 (33.3%) | ||
SEPT9mr | 0.032 (0.023–0.043) | 0.023 (0.018–0.029) | 0.033 | 0.97 (0.92, 1.00) |
Tumor size (cm) | 4.9 (4.0–6.7) | 4.0 (2.9–4.5) | 0.026 | 0.55 (0.30, 0.88) |
T | 0.748 | |||
T2 | 1 (8.3%) | 1 (3.7%) | ||
T3 | 8 (66.7%) | 23 (85.2%) | ||
T4 | 3 (25.0%) | 3 (11.1%) | ||
N | 0.368 | |||
N0 | 0 (0.0%) | 4 (14.8%) | ||
N1 | 6 (50.0%) | 14 (51.9%) | ||
N2 | 6 (50.0%) | 9 (33.3%) |
SEPT9mr | Probability of cTR | Tumor Size (cm) | Probability of cTR |
---|---|---|---|
0.00 | 0.879 | 0.0 | 0.969 |
0.01 | 0.835 | 0.5 | 0.958 |
0.02 | 0.780 | 1.0 | 0.944 |
0.03 | 0.712 | 1.5 | 0.925 |
0.04 | 0.633 | 2.0 | 0.902 |
0.05 | 0.547 | 2.5 | 0.871 |
0.06 | 0.457 | 3.0 | 0.833 |
0.07 | 0.370 | 3.5 | 0.787 |
0.08 | 0.291 | 4.0 | 0.731 |
0.09 | 0.223 | 4.5 | 0.668 |
0.10 | 0.167 | 5.0 | 0.597 |
0.11 | 0.122 | 5.5 | 0.523 |
0.12 | 0.089 | 6.0 | 0.447 |
0.13 | 0.064 | 6.5 | 0.374 |
0.14 | 0.045 | 7.0 | 0.306 |
0.15 | 0.032 | 7.5 | 0.245 |
8.0 | 0.194 | ||
8.5 | 0.151 | ||
9.0 | 0.116 | ||
9.5 | 0.088 | ||
10.0 | 0.067 |
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Domínguez-Prieto, V.; León-Arellano, M.; Olivera-Salazar, R.; Vega-Clemente, L.; Caramés, C.; Ruiz-Hispán, E.; Fuentes-Mateos, R.; Rosero-Rodríguez, D.; Guadalajara, H.; García-Arranz, M.; et al. Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer. Cancers 2025, 17, 965. https://doi.org/10.3390/cancers17060965
Domínguez-Prieto V, León-Arellano M, Olivera-Salazar R, Vega-Clemente L, Caramés C, Ruiz-Hispán E, Fuentes-Mateos R, Rosero-Rodríguez D, Guadalajara H, García-Arranz M, et al. Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer. Cancers. 2025; 17(6):965. https://doi.org/10.3390/cancers17060965
Chicago/Turabian StyleDomínguez-Prieto, Víctor, Miguel León-Arellano, Rocío Olivera-Salazar, Luz Vega-Clemente, Cristina Caramés, Eva Ruiz-Hispán, Raquel Fuentes-Mateos, Diana Rosero-Rodríguez, Héctor Guadalajara, Mariano García-Arranz, and et al. 2025. "Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer" Cancers 17, no. 6: 965. https://doi.org/10.3390/cancers17060965
APA StyleDomínguez-Prieto, V., León-Arellano, M., Olivera-Salazar, R., Vega-Clemente, L., Caramés, C., Ruiz-Hispán, E., Fuentes-Mateos, R., Rosero-Rodríguez, D., Guadalajara, H., García-Arranz, M., & García-Olmo, D. (2025). Pre-Treatment SEPTIN9 Gene Methylation Ratio Predicts Tumor Response to Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer. Cancers, 17(6), 965. https://doi.org/10.3390/cancers17060965