Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy?
Abstract
:1. Introduction
2. Results
2.1. Clinical–Pathological Characteristics of Patients
2.2. Clinical–Pathological Factors and Chemotherapy Response as Survival Markers
2.3. Analysis of ENT1, NOTCH3 mRNA, and miR-21 Levels in PDAC Tissue and Their Association with DSS
2.4. Immunostaining of ENT1 in FFPE Samples of PDAC
2.5. Analysis of ENT1 Transcripts in Subgroups with Negative, Low, and High ENT1 Protein Expression Analyzed by Immunohistochemistry
2.6. Analysis of Patients’ DSS Association with ENT1, NOTCH3 mRNA, and miR-21 Levels in Patients’ Subgroups, Defined by Clinical–Pathological Characteristics
2.7. Quantitative RT-PCR Analysis of ENT1, NOTCH3 mRNA, and miR-21 Expression in FFPE Samples of PDAC
3. Discussion
4. Materials and Methods
4.1. Patients and Pancreatic Cancer Staging
4.2. Preparation of Formalin-Fixed Paraffin-Embedded Samples of Pancreas
4.3. Extraction of mRNA from FFPE Samples and Reverse Transcription
4.4. Quantitative Analysis of ENT1, NOTCH3, and miR-21 Expression
4.5. Immunohistochemical Analysis of ENT1 Expression
4.6. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Number of Patients | 69 |
Gender (females/males) | 31/38 |
Age (years) | |
Median | 65 |
Range | 39–80 |
Surgery (type of resection) | |
PD | 55 |
DP | 14 |
Resection margin status | |
R0 | 46 |
R1 | 23 |
T: stage of primary tumor | |
T1 | 3 |
T2 | 12 |
T3 | 53 |
T4 | 1 |
N: regional lymph nodes | |
N0 | 19 |
N1 | 50 |
M: distant metastasis | |
M0 | 68 |
M1 | 1 |
DSS from surgery (months) | |
Median | 21 |
Range | 5–152 |
ASA (I-III) | |
I | 1 |
II | 42 |
III | 26 |
Patient Stratification | p Value | Hazard Ratio | 95.0% CI | |
---|---|---|---|---|
Gender (male) | 0.918 | 0.970 | 0.543 | 1.731 |
ENT1 (above median) | 0.821 | 0.934 | 0.514 | 1.695 |
Resection margin status (R1) | 0.135 | 0.624 | 0.336 | 1.159 |
ASA score | ||||
ASA III (reference value) | 0.601 | |||
ASA I | 0.421 | 2.395 | 0.286 | 20.063 |
ASA II | 0.639 | 0.869 | 0.484 | 1.561 |
Primary tumor stage | ||||
T4 (reference value) | 0.272 | |||
T1 | 0.434 | 0.354 | 0.026 | 4.786 |
T2 | 0.182 | 0.212 | 0.022 | 2.068 |
T3 | 0.106 | 0.169 | 0.019 | 1.463 |
Regional lymph nodes (N1) | 0.149 | 0.591 | 0.289 | 1.207 |
Resection type (DP) | 0.675 | 1.159 | 0.582 | 2.309 |
Patient Stratification | p Value | Hazard Ratio | 95.0% CI | |
---|---|---|---|---|
Gender (male) | 0.956 | 0.984 | 0.553 | 1.751 |
NOTCH3 (above median) | 0.383 | 1.286 | 0.731 | 2.263 |
Resection margin status (R1) | 0.126 | 0.614 | 0.328 | 1.147 |
ASA score | ||||
ASA III (reference value) | 0.725 | |||
ASA I | 0.484 | 2.120 | 0.259 | 17.379 |
ASA II | 0.773 | 0.915 | 0.501 | 1.671 |
Primary tumor stage | ||||
T4 (reference value) | 0.299 | |||
T1 | 0.507 | 0.424 | 0.034 | 5.358 |
T2 | 0.267 | 0.275 | 0.028 | 2.686 |
T3 | 0.144 | 0.200 | 0.023 | 1.728 |
Regional lymph nodes (N1) | 0.152 | 0.598 | 0.296 | 1.209 |
Resection type (DP) | 0.661 | 1.163 | 0.593 | 2.283 |
Patient Stratification | p Value | Hazard Ratio | 95.0% CI | |
---|---|---|---|---|
Gender (male) | 0.817 | 0.935 | 0.530 | 1.649 |
miR-21 (above median) | 0.089 | 0.475 | 0.201 | 1.120 |
Resection margin status (R1) | 0.113 | 0.604 | 0.324 | 1.126 |
ASA score | ||||
ASA III (reference value) | 0.587 | |||
ASA I | 0.477 | 2.138 | 0.263 | 17.375 |
ASA II | 0.530 | 0.828 | 0.460 | 1.491 |
Primary tumor stage | ||||
T4 (reference value) | 0.091 | |||
T1 | 0.280 | 0.237 | 0.017 | 3.234 |
T2 | 0.088 | 0.131 | 0.013 | 1.355 |
T3 | 0.036 | 0.085 | 0.009 | 0.846 |
Regional lymph nodes (N1) | 0.175 | 0.619 | 0.310 | 1.238 |
Resection type (DP) | 0.658 | 1.169 | 0.586 | 2.335 |
Patient Stratification | p Value | Hazard Ratio | 95.0% CI | |
---|---|---|---|---|
Gender (male) | 0.836 | 0.936 | 0.500 | 1.752 |
ENT1 | ||||
High (reference value) | 0.277 | |||
Negative | 0.471 | 1.469 | 0.517 | 4.174 |
Low | 0.109 | 1.800 | 0.877 | 3.695 |
Resection margin status (R1) | 0.051 | 0.505 | 0.254 | 1.003 |
ASA score | ||||
ASA III (reference value) | 0.592 | |||
ASA I | 0.768 | 1.385 | 0.159 | 12.091 |
ASA II | 0.367 | 0.747 | 0.396 | 1.408 |
Primary tumor stage | ||||
T4 (reference value) | 0.179 | |||
T1 | 0.637 | 0.513 | 0.032 | 8.162 |
T2 | 0.175 | 0.211 | 0.022 | 2.001 |
T3 | 0.075 | 0.138 | 0.016 | 1.222 |
Regional lymph nodes (N1) | 0.049 | 0.424 | 0.180 | 0.996 |
Resection type (DP) | 0.865 | 1.070 | 0.492 | 2.325 |
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Share and Cite
Jiraskova, L.; Ryska, A.; Duintjer Tebbens, E.J.; Hornychova, H.; Cecka, F.; Staud, F.; Cerveny, L. Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy? Cancers 2019, 11, 1621. https://doi.org/10.3390/cancers11111621
Jiraskova L, Ryska A, Duintjer Tebbens EJ, Hornychova H, Cecka F, Staud F, Cerveny L. Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy? Cancers. 2019; 11(11):1621. https://doi.org/10.3390/cancers11111621
Chicago/Turabian StyleJiraskova, Lucie, Ales Ryska, Erik Jurjen Duintjer Tebbens, Helena Hornychova, Filip Cecka, Frantisek Staud, and Lukas Cerveny. 2019. "Are ENT1/ENT1, NOTCH3, and miR-21 Reliable Prognostic Biomarkers in Patients with Resected Pancreatic Adenocarcinoma Treated with Adjuvant Gemcitabine Monotherapy?" Cancers 11, no. 11: 1621. https://doi.org/10.3390/cancers11111621