Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Tissue Sampling
2.2. Molecular Testing
2.3. Drug Sensitivity Analysis
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Molecular Profile
3.3. Correlations of Clinicopathological Characteristics and Mutation Profile with Overall Survival
3.4. Drug Sensitivity Analysis
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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Variable | Frequency |
---|---|
Gender | |
Female | 32 (50.8%) |
Male | 31 (49.2%) |
Age | |
Mean (SD) | 63.3 (12.4) |
Median [Min, Max] | 66.4 [30.4, 81.8] |
Histology | |
Adenocarcinoma | 57 (90.5%) |
Adenocarcinoma Mucinous | 6 (9.5%) |
Localization | |
Left | 46 (73.0%) |
Right | 15 (17.5%) |
N.D. * | 2 (3.2%) |
Liver metastases | |
Yes | 46 (73.0%) |
No | 14 (22.2%) |
N.D. * | 3 (4.8%) |
Colectomy | |
Yes | 56 (88.9%) |
No | 7 (11.1%) |
Metastasectomy | |
Yes | 27 (42.9%) |
No | 21 (33.3%) |
N.D. * | 15 (23.8%) |
Radiotherapy | |
Yes | 11 (17.5%) |
No | 52 (82.5%) |
Monoclonal antibodies therapy | |
Yes | 14 (22.2%) |
No | 49 (77.8%) |
First line of treatment | |
CapeOx | 26 (41.3%) |
Folfox | 32 (50.8%) |
Folfiri | 5 (7.9) |
Second line of treatment (FOLFOX or FOLFIRI) | |
Yes | 37 (56.8%) |
No | 26 (41.3%) |
Variable | Frequency |
---|---|
TYMS 3′UTR 6bp ins-del (rs151264360) | |
DEL/DEL | 31 (49.2%) |
INS/DEL | 32 (50.8%) |
GSTP1 c.313A>G (rs1695) | |
A/A | 20 (31.7%) |
G/A | 28 (44.4%) |
G/G | 15 (23.8%) |
DPYD c.1905+1 G>A (DPYD*2) (rs3918290) | |
G/G | 63 (100%) |
G/A | 0 (0%) |
A/A | 0 (0%) |
c.2846A>T (rs67376798) | |
A/A | 1 (1.6%) |
T/A | 1 (1.6%) |
T/T | 61 (96.8%) |
c.1679T>G (DPYD*13) (rs55886062) | |
T/T | 63 (100%) |
T/G | 0 (0%) |
G/G | 0 (0%) |
c.85T>C (DPYD*9) (rs1801265) | |
T/T | 37 (58.7%) |
C/T | 19 (30.2%) |
C/C | 6 (9.5%) |
N.D. | 1 (1.6%) |
ABCB1 c.3435C>T (rs1045642) | |
T/T | 9 (14.3%) |
C/T | 31 (49.2%) |
C/C | 21 (33.3%) |
N.D. | 2 (3.2%) |
c.1236 T>C (rs1128503) | |
T/T | 6 (9.5%) |
C/T | 41 (65.1%) |
C/C | 15 (23.8%) |
N.D | 1 (1.6%) |
ABCC2 c.-24C>T (rs717620) | |
C/C | 46 (73.0%) |
C/T | 11 (17.5%) |
T/T | 2 (3.2%) |
N.D. | 4 (6.3%) |
MTHFR c.1409A>C (rs1801131) | |
A/A | 33 (52.4%) |
A/C | 21 (33.3%) |
C/C | 8 (12.7%) |
N.D. | 1 (1.6%) |
Tumor Mutation | Frequency |
---|---|
BRAF | |
Mutated (V600E) | 7 (11.1%) |
Wild-type | 58 (88.9%) |
KRAS mutations * | |
Mutated | 22 (34.9%) |
Wild-type | 41 (65.1%) |
NRAS mutations ** | |
Mutated | 7 (11.1%) |
Wild-type | 56 (88.9%) |
PI3KCA mutations *** | |
Mutated | 7 (11.1%) |
Wild-type | 56 (88.9%) |
AKT1 E17K | |
Mutated | 2 (3.2%) |
Wild-type | 61 (96.8%) |
Variables | Patients (n) | HR | 95% CI Lower-Upper | p-Value ** |
---|---|---|---|---|
Liver metastases | ||||
Yes | 46 | 3.51 | 1.52–8.07 | 0.003 |
No | 14 | Ref. | ||
Colectomy | ||||
Yes | 56 | 0.480 | 0.214–1.08 | 0.079 |
No | 7 | Ref. | ||
GSTP1 rs1695 | ||||
Yes (G/G) | 15 | 0.484 | 0.234–1.00 | 0.05 |
No (G/A+A/A) | 48 | Ref. | ||
DPYD rs1801265 | ||||
Yes (C/C + C/T) | 25 | 1.819 | 1.03–3.19 | 0.0377 |
No (T/T) | 37 | Ref. | ||
ABCB1 rs1045642 | ||||
Yes C/C | 21 | 1.782 | 1.00–3.16 | 0.0483 |
No (C/T+T/T) | 40 | Ref. | ||
MTHFR rs180113 | ||||
Yes C/C | 6 | 2.295 | 1.05–4.97 | 0.0352 |
No (A/C+A/A) | 54 | Ref. | ||
TYMS rs151264360 | ||||
Yes Ins/Del | 32 | 2.169 | 1.21–3.86 | 0.0087 |
No Del/Del | 31 | Ref. | ||
Mutated PI3KCA | ||||
Yes | 7 | 0.271 | 0.084–0.876 | 0.0292 |
No | 56 | Ref. | ||
BRAF | ||||
Wild-type | 56 | 0.28 | 0.087–0.909 | 0.034 |
Mutated (V600E) | 7 | Ref. | ||
High-Risk Profile *** | ||||
Yes | 41 | 2.06 | 1.13–3.74 | 0.018 |
No | 21 | Ref. | ||
High-Risk Profile *** + BRAF wild-type patients | ||||
Yes | 38 | 2.80 | 1.55–5.06 | <0.005 |
No | 25 | Ref. |
Variables | Patients (n) | HR | 95% CI Lower-Upper | p-Value * |
---|---|---|---|---|
Liver metastases | ||||
Yes | 45 | 3.69 | 1.49–9.09 | 0.004 |
No | 13 | Ref. | ||
DPYDrs1801265 | ||||
Yes (C/C + C/T) | 23 | 1.88 | 0.99–3.54 | 0.052 |
No (T/T) | 35 | |||
ABCB1 rs1045642 | ||||
Yes C/C | 20 | 2.62 | 1.37–4.99 | 0.003 |
No C/T + T/T | 38 | Ref. | ||
MTHFR rs180113 | ||||
Yes C/C | 8 | 2.63 | 1.13–6.15 | 0.004 |
No A/C + A/A | 50 | Ref. |
a. High-Risk Profile * and BRAF V600E Mutation. | ||||
---|---|---|---|---|
Variables | Patients (n) | HR | 95% CI Lower-Upper | p-Value ** |
High-risk presence | ||||
Yes | 38 | 2.18 | 1.15–4.11 | 0.017 |
No | 20 | Ref. | ||
Liver metastases | ||||
Yes | 45 | 3.34 | 1.39–8.05 | 0.006 |
No | 13 | Ref | ||
BRAF V600E | ||||
Mutated | 7 | 0.41 | 0.12–1.39 | 0.153 |
Wild-type | 51 | Ref. | ||
b. High-risk profile * and KRAS mutation. | ||||
Variables | Patients (n) | HR | 95% CI Lower-Upper | p-value ** |
High-risk presence | ||||
Yes | 38 | 2.28 | 1.20–4.33 | 0.012 |
No | 20 | Ref. | ||
Liver metastases | ||||
Yes | 45 | 4.71 | 1.91–11.6 | <0.005 |
No | 13 | Ref | ||
KRAS | ||||
Mutated | 21 | 0.59 | 0.31–1.11 | 0.105 |
Wild-type | 37 | Ref. | ||
c. High-risk profile * and PI3KCA mutation. | ||||
Variables | Patients (n) | HR | 95% CI Lower-Upper | p-value ** |
High-risk presence | ||||
Yes | 38 | 2.43 | 1.26–4.66 | 0.007 |
No | 20 | Ref. | ||
Liver metastases | ||||
Yes | 45 | 4.08 | 1.68–9.86 | 0.002 |
No | 13 | Ref | ||
PI3KCA | ||||
Mutated | 6 | 0.22 | 0.05–0.95 | 0.042 |
Wild-type | 52 | Ref. |
Variables | Patients (n) | HR | 95% CI Lower-Upper | p-Value * |
---|---|---|---|---|
High-risk ** + BRAF wild-type patients | ||||
Yes | 35 | 2.71 | 1.46–5.01 | 0.001 |
No | 23 | Ref. | ||
Liver metastases | ||||
Yes | 45 | 3.55 | 1.52–8.29 | 0.003 |
No | 13 | Ref |
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Cayún, J.P.; Cerpa, L.C.; Colombo, A.; Cáceres, D.D.; Leal, J.L.; Reyes, F.; Gutiérrez-Cáceres, C.; Calfunao, S.; Varela, N.M.; Quiñones, L.A. Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study. Curr. Oncol. 2024, 31, 274-295. https://doi.org/10.3390/curroncol31010018
Cayún JP, Cerpa LC, Colombo A, Cáceres DD, Leal JL, Reyes F, Gutiérrez-Cáceres C, Calfunao S, Varela NM, Quiñones LA. Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study. Current Oncology. 2024; 31(1):274-295. https://doi.org/10.3390/curroncol31010018
Chicago/Turabian StyleCayún, Juan Pablo, Leslie Carol Cerpa, Alicia Colombo, Dante Daniel Cáceres, José Luis Leal, Felipe Reyes, Carolina Gutiérrez-Cáceres, Susan Calfunao, Nelson Miguel Varela, and Luis Abel Quiñones. 2024. "Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study" Current Oncology 31, no. 1: 274-295. https://doi.org/10.3390/curroncol31010018