The Level of Preoperative Plasma KRAS Mutations and CEA Predict Survival of Patients Undergoing Surgery for Colorectal Cancer Liver Metastases
Abstract
:1. Introduction
2. Results
2.1. The Presence and the Level of KRAS Mutations in Tissue of Primary Tumor and Liver Metastases
2.2. The Presence and the Level of KRAS Mutations in Plasma
2.3. The Preoperative and Postoperative Serum Level of CEA in Patients Undergoing Liver Surgery
2.4. Survival Analysis
3. Discussion
4. Materials and Methods
4.1. Patients and Samples
4.2. Blood Samples
4.3. DNA Isolation
4.4. ddPCR Assay
4.5. Quantitative Measurement of CEA
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
95% CI | 95% Confidence interval |
CEA | Carcinoembryonic antigen |
CLM | Colorectal cancer liver metastases |
CRC | Colorectal cancer |
CTC | Circulating tumor cells |
cfDNA | Circulating cell-free deoxyribonucleic acid |
ctDNA | Circulating cell-free tumor deoxyribonucleic acid |
ddPCR | Droplet digital polymerase chain reaction |
DFS | Disease-free survival |
DMFS | Distant metastasis free survival |
DNA | Deoxyribonucleic acid |
EGFR | Epidermal growth factor receptor |
FFPE | Formalin-fixed, paraffin-embedded |
FPR | False positive rate |
HR | Hazard ratio |
IUCC | International union against cancer |
KRAS | Kirsten rat sarcoma viral oncogene homolog |
mAb | Monoclonal antibody |
miRNA | Micro-ribonucleic acid |
NRAS | Neuroblastoma RAS viral oncogene homolog |
OS | Overall survival |
PCR | Polymerase chain reaction |
pFA | Plasma KRAS fractional abundance |
pKRAS- | Plasma KRAS negativity |
pKRAS+ | Plasma KRAS positivity |
RECIST | Response evaluation criteria in solid tumors |
RFA | Radiofrequency ablation |
tFA | Tissue KRAS fractional abundance |
tKRAS+ | Tissue KRAS positivity |
TNM | Tumor, node, metastases |
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Tissue Origin | CRC | ||
---|---|---|---|
KRAS Status | KRAS Negative | KRAS Positive | |
CLM | KRAS negative | 28 | 3 |
KRAS positive | 1 | 29 |
Tissue vs. Plasma Origin | CLM Tissue | ||
---|---|---|---|
KRAS Status | KRAS Negative | KRAS Positive | |
Plasma | KRAS negative | 12 | 6 |
KRAS positive | 1 | 10 |
The Multivariate Survival Analysis | DFS | OS | ||
---|---|---|---|---|
Status of Biomarkers and Clinical Characteristics | HR (95% Confidence Interval) | Significance | HR (95% Confidence Interval) | Significance |
Plasma KRAS fractional abundance [cut-off 3.33%] | ||||
Low level | 1.000 | 1.000 | ||
High level | 2.542 (0.823–7.853) | p = 0.105 | 11.732 (2.729–50.432) | p= 0.001 |
CEA [cut-off 4.9 µg/L] | ||||
Low level | 1.000 | 1.000 | ||
High level | 3.264 (1.119–9.521) | p= 0.03 | 5.409 (1.272–22.998) | p= 0.022 |
Extend of liver resection | ||||
R0 | 1.000 | 1.000 | ||
R1 | 3.309 (1.09–10.045) | p= 0.035 | 6.054 (1.499–24.451) | p= 0.011 |
RFA 1 | 2.895 (0.891–9.406) | p = 0.077 | 7.368 (1.479–36.7) | p= 0.015 |
Biological treatment | ||||
bevacizumab or cetuximab | 1.000 | 1.000 | ||
n.a. | 1.546 (0.633–3.774) | p = 0.339 | 0.828 (0.326–2.104) | p = 0.692 |
Patient Characteristics | Number of Patients (%) |
---|---|
All patients in the study | 71 (100%) |
Gender | |
Female | 29 (41%) |
Male | 42 (59%) |
Mean age at liver surgery (min-max) | 62.7 (29–77) years |
Extent of liver surgery | |
R0 resection | 38 (54%) |
R1 resection | 21 (30%) |
RFA 1 | 11 (16%) |
Adjuvant chemotherapy | |
Yes | 55 (77%) |
No | 16 (23%) |
Adjuvant biological therapy (bevacizumab or cetuximab) | |
Yes | 15 (21%) |
No | 56 (79%) |
Tumor grade (available in 44 pts.) | |
Grade 1 | 15 (21%) |
Grade 2 | 23 (32%) |
Grade 3 | 6 (9%) |
Number of liver metastases | |
1 | 35 (49%) |
≥2 | 36 (51%) |
Mean size of metastases (min-max) | 38.5 (6–130) mm |
Extrahepatic disease | |
Yes | 4 (6%) |
No | 67 (94%) |
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Share and Cite
Polivka, J.; Windrichova, J.; Pesta, M.; Houfkova, K.; Rezackova, H.; Macanova, T.; Vycital, O.; Kucera, R.; Slouka, D.; Topolcan, O. The Level of Preoperative Plasma KRAS Mutations and CEA Predict Survival of Patients Undergoing Surgery for Colorectal Cancer Liver Metastases. Cancers 2020, 12, 2434. https://doi.org/10.3390/cancers12092434
Polivka J, Windrichova J, Pesta M, Houfkova K, Rezackova H, Macanova T, Vycital O, Kucera R, Slouka D, Topolcan O. The Level of Preoperative Plasma KRAS Mutations and CEA Predict Survival of Patients Undergoing Surgery for Colorectal Cancer Liver Metastases. Cancers. 2020; 12(9):2434. https://doi.org/10.3390/cancers12092434
Chicago/Turabian StylePolivka, Jiri, Jindra Windrichova, Martin Pesta, Katerina Houfkova, Hana Rezackova, Tereza Macanova, Ondrej Vycital, Radek Kucera, David Slouka, and Ondrej Topolcan. 2020. "The Level of Preoperative Plasma KRAS Mutations and CEA Predict Survival of Patients Undergoing Surgery for Colorectal Cancer Liver Metastases" Cancers 12, no. 9: 2434. https://doi.org/10.3390/cancers12092434