The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Procedures for Sample Analyses
2.3. Statistical Analyses
3. Results
3.1. Clinicopathological Characteristics of Patients
3.2. NLR and PLR Are Prognostic Markers in Metastatic PDAC Patients
3.3. Combined Analysis of NLR and PLR Improves the Prognostic Accuracy in Patients with Metastatic PDAC
3.4. The Combination of NLR and cfDNA Values Significantly Improves Prognostic Stratification of Metastatic PDAC Patients
3.5. NLR Is Related to RAS Mutational Status in cfDNA of Metastatic PDAC Patients
3.6. Multiple Blood-Based Biomarkers Improve the Prognostic Stratification of Metastatic PDAC Patients
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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Patient Characteristics | n (%) | |
---|---|---|
Age | <60 years | 20 (34.5) |
>60 years | 38 (65.5) | |
Sex | Male | 32 (55.2) |
Female | 26 (44.8) | |
ECOG | 0 | 17 (29.3) |
1 | 30 (51.7) | |
2 | 8 (13.8) | |
3 | 3 (5.2) | |
1st line treatment | Gemcitabine | 2 (3.4) |
Gemcitabine/nab-paclitaxel | 38 (65.5) | |
Gemcitabine/nab-paclitaxel/FOLFOX | 4 (6.9) | |
FOLFIRINOX | 11 (19) | |
No treatment | 3 (5.2) | |
Survival | Alive | 17 (29.3) |
Dead | 41 (70.7) | |
Disease progression | Yes | 50 (86.2) |
No | 3 (5.2) | |
Not valuable (No treatment or surgery) | 5 (8.6) | |
Primary tumor location | Tail | 16 (27.6) |
Body | 24 (41.4) | |
Head | 16 (27.6) | |
No data | 2 (3.4) | |
Number of metastatic lesions | One location | 25 (43.1) |
More than one location | 33 (56.9) | |
Metastatic lesions location | Hepatic lesions | 45 (77.6) |
Non-hepatic lesions | 13 (22.4) | |
Liquid Biopsy RAS status | RAS mutated | 44 (75.9) |
RAS wild-type | 14 (24.1) |
Variables | OS | PFS | ||
---|---|---|---|---|
HR (95%CI) | p | HR (95%CI) | p | |
Age | ||||
≤60 years | 1.113 (0.584–2.119) | 0.7452 | 0.925 (0.505–1.694) | 0.8015 |
>60 years | ||||
Gender | ||||
Male | 0.545 (0.291–1.019) | 0.0574 | 0.615 (0.343–1.106) | 0.1044 |
Female | ||||
ECOG | ||||
0 | 0.0030 | 0.1869 | ||
1 | 1.653 (0.789–3.465) | 1.083 (0.568–2.065) | ||
2–3 | 5.967 (1.86–19.16) | 3.166 (0.978–10.25) | ||
Primary Tumor Location | ||||
Body/Tail | 1.48 (0.72–3.04) | 0.2884 | 1.52 (0.74–3.10) | 0.2500 |
Head | ||||
Number of Metastasis | ||||
1 | 1.5 (0.803–2.801) | 0.2035 | 1.449 (0.811–2.588) | 0.2100 |
≥2 | ||||
Metastatic Location | ||||
Hepatic | 0.462 (0.234–0.913) | 0.0262 | 0.344 (0.187–0.634) | 0.0006 |
Nonhepatic | ||||
RAS mutation status plasma | ||||
MUT | 0.283 (0.141–0.565) | 0.0003 | 0.240 (0.126–0.458) | <0.0001 |
WT | ||||
NLR | ||||
≤5.52 | 5.881 (2.552–13.55) | <0.0001 | 2.754 (1.272–5.962) | 0.0101 |
>5.52 | ||||
PLR | ||||
≤90.48 | 1.816 (0.817–4.035) | 0.1430 | 1.460 (0.718–2.972) | 0.2960 |
>90.48 | ||||
cfDNA concentration | ||||
≤26.46 ng/mL | 2.173 (1.149–4.107) | 0.0169 | 1.708 (0.964–3.025) | 0.0664 |
>26.46 ng/mL | ||||
MAF | ||||
≤0.351% | 2.151 (1.049–4.409) | 0.0365 | 1.859 (0.925–3.737) | 0.0818 |
>0.351% | ||||
CA19-9 | ||||
≤45,500 U/mL | 3.514 (1.196–10.32) | 0.0233 | 3.508 (1.334–9.227) | 0.0110 |
>45,500 U/mL |
Variables | OS | PFS | ||
---|---|---|---|---|
HR (95%CI) | p | HR (95%CI) | p | |
ECOG | 2.024 (1.207–3.393) | 0.008 | - | - |
Metastatic Location | - | ns | 3.150 (1.359–7.305) | 0.007 |
RAS mutation status plasma | 6.944 (2.033–23.73) | 0.002 | 7.908 (2.482–25.20) | 0.0001 |
NLR | 2.466 (1.246–4.880) | 0.010 | - | ns |
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Toledano-Fonseca, M.; Cano, M.T.; Inga, E.; Gómez-España, A.; Guil-Luna, S.; García-Ortiz, M.V.; Mena-Osuna, R.; De la Haba-Rodriguez, J.R.; Rodríguez-Ariza, A.; Aranda, E. The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer. Cancers 2021, 13, 1210. https://doi.org/10.3390/cancers13061210
Toledano-Fonseca M, Cano MT, Inga E, Gómez-España A, Guil-Luna S, García-Ortiz MV, Mena-Osuna R, De la Haba-Rodriguez JR, Rodríguez-Ariza A, Aranda E. The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer. Cancers. 2021; 13(6):1210. https://doi.org/10.3390/cancers13061210
Chicago/Turabian StyleToledano-Fonseca, Marta, M. Teresa Cano, Elizabeth Inga, Auxiliadora Gómez-España, Silvia Guil-Luna, María Victoria García-Ortiz, Rafael Mena-Osuna, Juan R. De la Haba-Rodriguez, Antonio Rodríguez-Ariza, and Enrique Aranda. 2021. "The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer" Cancers 13, no. 6: 1210. https://doi.org/10.3390/cancers13061210