Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Size Calculation
2.2. Sera from CCA Patients and HC
2.3. Prediction of Secretory Proteins
2.4. Western Blot Analysis
2.5. Dot Blot Assay and Data Acquisition
2.6. Statistical Analysis
3. Results
3.1. Bioinformatic Analysis of AIFM3 Protein to Predict its Secretory Protein Nature
3.2. AIFM3 Expression in the Serum Samples
3.3. Serum AIFM3 Levels of CCA and HC
3.4. Correlation between AIFM3 Expression in Serum and CCA Tissues
3.5. The Correlation of Serum AIFM3 Levels with Clinical Parameters
3.6. Evaluation of the Prognostic Potential of Serum AIFM3 in Comparison with other Prognostic Markers
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameter (Normal Range) | HC (n = 70) | CCA (n = 141) | p-Value |
---|---|---|---|
Age | 41 ± 7 | 60 ± 6.5 a | * <0.001 |
(19–85) | (31–76) | ||
Total protein | NA | 7.5 ± 0.5 b | NA |
(6.5–8.8 g/dL) | (4.6–10) | ||
Total bilirubin | NA | 0.6 ± 0.8 b | NA |
(0.25–1.5) | (0.2–24.9) | ||
Direct bilirubin | NA | 0.3 ± 0.6 b | NA |
(0–0.5 mg/dL) | (0–13.7) | ||
ALT | 21 ± 6 | 38 ± 20 b | * <0.001 |
(4–36 U/L) | (4–36) | (1–795) | |
AST | 20 ± 4 | 40 ± 18.7 b | * <0.001 |
(12–32 U/L) | (6–34) | (4–1112) | |
ALP | 47 ± 9 | 168 ± 79 b | * <0.001 |
(42–121 U/L) | (27–98) | (35–1068) | |
Serum AIFM3 levels (ng/µL) | 3.258 ± 2.671 | 8.419 ± 7.269 c | * <0.001 |
(0.001–9.602) | (0.175–28.907) | ||
CA19-9 | NA | 67.7 ± 435.8 d | NA |
(0–37 U/mL) | (0.6–1000) | ||
CEA | NA | 5.1 ± 4.7 e | NA |
(0–2.5 ng/mL) | (0.9–917.6) |
Clinical Parameters | No. | Serum AIFM3 Levels (ng/µL) | ||
---|---|---|---|---|
≤8.292 | >8.292 | p-Value a | ||
Gender (n = 136) | ||||
Male | 91 | 62 (45.5%) | 29 (21.3%) | 0.701 |
Female | 45 | 26 (19.1%) | 19 (14.1%) | |
Lymph node metastasis (n = 137) | ||||
No | 62 | 50 (36.4%) | 12 (8.7%) | * 0.001 |
Yes | 75 | 40 (29.1%) | 35 (25.8%) | |
Age (Years) | 136 | 58.2 ± 9.5 | 63.2 ± 6.9 | * 0.002 b |
(n = 89) | (n = 42) | |||
Total protein (g/dL) | 131 | 7.3 ± 1.1 | 7.7 ± 0.8 | 0.094 |
(n = 89) | (n = 42) | |||
Total bilirubin (mg/dL) | 131 | 2.1 ± 4.1 | 1.3 ± 1.7 | 0.250 |
(n = 89) | (n = 42) | |||
Direct bilirubin (mg/dL) | 131 | 1.4 ± 2.6 | 0.9 ± 1.6 | 0.395 |
(n = 89) | (n = 42) | |||
ALT (U/L) | 131 | 69.7 ± 112.4 | 45.7 ± 38.9 | 0.475 |
(n = 89) | (n = 42) | |||
AST (U/L) | 131 | 88.6 ± 174.1 | 49.8 ± 38.2 | 0.624 |
(n = 89) | (n = 42) | |||
ALP (U/L) | 131 | 247.3 ± 191.7 | 209.9 ± 200.7 | 0.067 |
(n = 89) | (n = 42) | |||
Survival time (days) | 139 | 579.8 ± 649.6 | 358.0 ± 185.4 | * 0.017 b |
(n = 87) | (n = 52) |
Clinicopathological Factors | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Lymph node metastasis | 1.13 (0.84–1.95) | 0.279 | 1.38 (0.96–2.14) | 0.103 |
(non-metastasis or metastasis) | ||||
Histological grading | 1.10 (0.56–1.21) | 0.567 | 0.99 (0.47–1.23) | 0.721 |
(non-papillary or papillary) | ||||
Gender (female or male) | 1.20 (0.71–1.65) | 0.731 | 1.35 (0.65–1.27) | 0.610 |
Age (≤60 or >60 yr) | 1.07 (0.88–2.01) | 0.345 | 1.16 (0.61–2.21) | 0.442 |
Total protein | 0.84 (0.56–1.24) | 0.239 | 0.95 (0.50–1.41) | 0.357 |
(≤8.8 or >8.8 g/dL) | ||||
Total bilirubin | 1.09 (0.64–1.88) | 0.704 | 1.42 (0.65–2.59) | 0.562 |
(≤1.5 or >1.5 mg/dL) | ||||
Direct bilirubin | 0.96 (0.67–1.59) | 0.847 | 0.78 (0.31–1.99) | 0.694 |
(≤0.5 or >0.5 mg/dL) | ||||
ALT (≤36 or >36 U/L) | 1.22 (0.90–2.02) | 0.265 | 1.44 (0.99–2.72) | 0.331 |
AST (≤32 or >32 U/L) | 1.28 (0.94–1.81) | 0.546 | 1.07 (0.83–2.47) | 0.664 |
ALP (≤121 or >121 U/L) | 1.30 (0.84–1.45) | 0.567 | 1.45 (0.97–2.49) | 0.704 |
AIFM3 levels | 1.98 (1.28–3.26) | * 0.015 | 3.15 (1.92–6.37) | * 0.009 |
(≤8.292 or >8.292 ng/µL) |
Tumor Markers | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
AIFM3 (cut-off 8.292 ng/µL) | 1.98 (1.28–3.26) | * 0.015 | 3.15 (1.92–6.37) | * 0.009 |
CA19-9 (cut-off 900 U/mL) | 1.21 (0.61–2.50) | 0.361 | 1.39 (0.81–2.41) | 0.240 |
CEA (cut-off 5.5 ng/mL) | 1.57 (1.02–2.40) | * 0.038 | 1.81 (0.90–3.25) | 0.088 |
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Chua-on, D.; Proungvitaya, T.; Tummanatsakun, D.; Techasen, A.; Limpaiboon, T.; Roytrakul, S.; Wongkham, S.; Wongkham, C.; Somintara, O.; Sangkhamanon, S.; et al. Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients. Biomolecules 2020, 10, 1021. https://doi.org/10.3390/biom10071021
Chua-on D, Proungvitaya T, Tummanatsakun D, Techasen A, Limpaiboon T, Roytrakul S, Wongkham S, Wongkham C, Somintara O, Sangkhamanon S, et al. Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients. Biomolecules. 2020; 10(7):1021. https://doi.org/10.3390/biom10071021
Chicago/Turabian StyleChua-on, Daraporn, Tanakorn Proungvitaya, Doungdean Tummanatsakun, Anchalee Techasen, Temduang Limpaiboon, Sittiruk Roytrakul, Sopit Wongkham, Chaisiri Wongkham, Ongart Somintara, Sakkarn Sangkhamanon, and et al. 2020. "Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients" Biomolecules 10, no. 7: 1021. https://doi.org/10.3390/biom10071021