Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer
Abstract
:1. Introduction
2. Results
2.1. Study Cohort
2.2. DNA Sequencing
2.2.1. MSS Samples Analysis
2.2.2. Additional Analyses
2.3. RNA Sequencing
3. Discussion
3.1. Patient Characteristics and Clinicopathological Variables
3.2. DNA and RNA Sequencing
3.3. Treatment Options and Future Perspectives
3.4. Strengths and Limitations
4. Materials and Methods
4.1. Patients
4.2. Tumor Samples
4.3. TruSight Oncology 500 Analysis
4.4. Statistical Analysis
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 | M0 (N = 20) | LM (N = 10) | PM (N = 9) | p Value |
---|---|---|---|---|
Age at time of diagnosis (years)—median (Q1–Q3) | 69.00 | 69.00 | 68.00 | 0.801 a |
(62.00–74.90) | (63.75–74.25) | (58.00–74.00) | ||
Gender–n (%) | 0.514 b | |||
Male | 12 (60) | 8 (80) | 5 (55.6) | |
Female | 8 (40) | 2 (20) | 4 (44.4) | |
Primary tumor location †—n (%) | 0.433 b | |||
Right colon | 10 (50) | 2 (20) | 2 (22.2) | |
Left colon | 7 (35) | 5 (50) | 4 (44.4) | |
Rectum | 3 (15) | 3 (30) | 3 (33.3) | |
Tumor size (cm) —median (Q1–Q3) | 4.10 | 2.25 | 3.00 | 0.061 a |
(3.28–5.38) | (1.80–5.43) | (2.40–3.50) | ||
Differentiation grade—n (%) * | <0.001 b | |||
Poor | 4 (20) | 0 (0) | 0 (0) | |
Poor/moderate | 2 (10) | 2 (20) | 8 (88.9) | |
Moderate | 14 (70) | 6 (60) | 1 (11.1) | |
Moderate/well | 0 (0) | 1 (10) | 0 (0) | |
Type of surgery—n (%) | 0.153 b | |||
Open | 10 (50) | 2 (20) | 5 (55.6) | |
Laparoscopic | 10 (50) | 6 (60) | 4 (44.4) | |
Robot assisted | 0 (0) | 2 (20) | 0 (0) | |
Positive lymph nodes—n (%) | 0.389 b | |||
No | 11 (55) | 8 (80) | 5 (55.6) | |
Yes | 9 (45) | 2 (20) | 4 (44.4) | |
Neoadjuvant treatment—n (%) | 0.039 b | |||
No | 17 (85) | 4 (40) | 7 (77.8) | |
Yes | 3 (15) | 6 (60) | 2 (22.2) | |
Adjuvant treatment—n (%) * | 0.247 b | |||
No | 9 (45) | 7 (70) | 4 (44.4) | |
Yes | 11 (55) | 2 (20) | 5 (55.6) | |
Oncological history—n (%) | 0.882 b | |||
No | 18 (90) | 8 (80) | 8 (88.9) | |
Yes | 2 (10) | 2 (20) | 1 (11.1) | |
Oncological family history—n (%) * | 1.000 b | |||
No | 6 (30) | 3 (30) | 0 (0) | |
Yes | 12 (60) | 5 (50) | 1 (11.1) | |
Time between surgery and metastases (months)—median (Q1–Q3) | N/A | 18.09 | 16.42 | 0.744 c |
(7.77–28.95) | (9.71–25.05) | |||
PCI score—median (Q1–Q3) | N/A | N/A | 3.50 | N/A |
(3.00–4.00) |
M Group | Gene Pair | Breakpoint 1 | Breakpoint 2 | Fusion Supporting Reads |
---|---|---|---|---|
M0 | TARSL2-NTRK3 | Exon 18 chr15:102197123 | Exon 14 chr15:88576274 | 19 |
PM | FAM198A-RAF1 | Exon not found chr3:43101459 | Exon 3 chr3:12653448 | 85 |
PM | RPS6KB1-HSF5 | Exon 1 chr17:57970685 | Exon 3 chr17:56544340 | 21 |
Inclusion Criteria | Exclusion Criteria |
---|---|
|
|
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Heuvelings, D.J.I.; Wintjens, A.G.W.E.; Moonen, L.; Engelen, S.M.E.; de Hingh, I.H.J.T.; Valkenburg-van Iersel, L.B.; den Dulk, M.; Beckervordersandforth, J.; Thijssen, S.G.M.; Leunissen, D.J.G.; et al. Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer. Int. J. Mol. Sci. 2023, 24, 12830. https://doi.org/10.3390/ijms241612830
Heuvelings DJI, Wintjens AGWE, Moonen L, Engelen SME, de Hingh IHJT, Valkenburg-van Iersel LB, den Dulk M, Beckervordersandforth J, Thijssen SGM, Leunissen DJG, et al. Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer. International Journal of Molecular Sciences. 2023; 24(16):12830. https://doi.org/10.3390/ijms241612830
Chicago/Turabian StyleHeuvelings, Danique J. I., Anne G. W. E. Wintjens, Laura Moonen, Sanne M. E. Engelen, Ignace H. J. T. de Hingh, Liselot B. Valkenburg-van Iersel, Marcel den Dulk, Jan Beckervordersandforth, Sharon G. M. Thijssen, Daphne J. G. Leunissen, and et al. 2023. "Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer" International Journal of Molecular Sciences 24, no. 16: 12830. https://doi.org/10.3390/ijms241612830