Circulatory MIC-1 as a Determinant of Prostate Cancer Racial Disparity
Abstract
Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Patients and Samples
2.2. Enzyme-Linked Immunosorbent Assay (ELISA)
2.3. Immunohistochemistry (IHC) and Evaluation of Immunohistochemical Staining
2.4. Statistical Analysis
3. Results
3.1. Univariate Analyses
3.2. Correlation Analyses
3.3. Multivariable Regression Models
3.4. Analysis of urine MIC-1
3.5. ROC Curve Analysis of Circulatory MIC-1
3.6. MIC-1 Protein Expression in Prostate Tumor Biopsies
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30. [Google Scholar] [CrossRef]
- Sundi, D.; Ross, A.E.; Humphreys, E.B.; Han, M.; Partin, A.W.; Carter, H.B.; Schaeffer, E.M. African american men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: Should active surveillance still be an option for them? J. Clin. Oncol. 2013, 31, 2991–2997. [Google Scholar] [CrossRef]
- Heaphy, C.M.; Joshu, C.E.; Barber, J.R.; Davis, C.; Zarinshenas, R.; De Marzo, A.M.; Lotan, T.L.; Sfanos, K.S.; Meeker, A.K.; Platz, E.A. Racial difference in prostate cancer cell telomere lengths in men with higher grade prostate cancer: A clue to the racial disparity in prostate cancer outcomes. Cancer Epidemiol. Biomark. Prev. 2020, 29, 676–680. [Google Scholar] [CrossRef]
- Tosoian, J.J.; Almutairi, F.; Morais, C.L.; Glavaris, S.; Hicks, J.; Sundi, D.; Humphreys, E.; Han, M.; De Marzo, A.M.; Ross, A.E.; et al. Prevalence and prognostic significance of pten loss in african-american and european-american men undergoing radical prostatectomy. Eur. Urol. 2017, 71, 697–700. [Google Scholar] [CrossRef]
- Liu, W.; Zhang, Y.; Wei, S.; Bae, S.; Yang, W.H.; Smith, G.J.; Mohler, J.L.; Fontham, E.T.H.; Bensen, J.T.; Sonpavde, G.P.; et al. A cd24-p53 axis contributes to african american prostate cancer disparities. Prostate 2020, 80, 609–618. [Google Scholar] [CrossRef]
- Khani, F.; Mosquera, J.M.; Park, K.; Blattner, M.; O’Reilly, C.; MacDonald, T.Y.; Chen, Z.; Srivastava, A.; Tewari, A.K.; Barbieri, C.E.; et al. Evidence for molecular differences in prostate cancer between african american and caucasian men. Clin. Cancer Res. 2014, 20, 4925–4934. [Google Scholar] [CrossRef]
- Hashimoto, Y.; Shiina, M.; Dasgupta, P.; Kulkarni, P.; Kato, T.; Wong, R.K.; Tanaka, Y.; Shahryari, V.; Maekawa, S.; Yamamura, S.; et al. Upregulation of mir-130b contributes to risk of poor prognosis and racial disparity in african-american prostate cancer. Cancer Prev. Res. 2019, 12, 585–598. [Google Scholar] [CrossRef]
- Khan, S.; Simpson, J.; Lynch, J.C.; Turay, D.; Mirshahidi, S.; Gonda, A.; Sanchez, T.W.; Casiano, C.A.; Wall, N.R. Racial differences in the expression of inhibitors of apoptosis (iap) proteins in extracellular vesicles (ev) from prostate cancer patients. PLoS ONE 2017, 12, e0183122. [Google Scholar] [CrossRef]
- Karan, D.; Chen, S.J.; Johansson, S.L.; Singh, A.P.; Paralkar, V.M.; Lin, M.F.; Batra, S.K. Dysregulated expression of mic-1/pdf in human prostate tumor cells. Biochem. Biophys. Res. Commun. 2003, 305, 598–604. [Google Scholar] [CrossRef]
- Selander, K.S.; Brown, D.A.; Sequeiros, G.B.; Hunter, M.; Desmond, R.; Parpala, T.; Risteli, J.; Breit, S.N.; Jukkola-Vuorinen, A. Serum macrophage inhibitory cytokine-1 concentrations correlate with the presence of prostate cancer bone metastases. Cancer Epidemiol. Biomark. Prev. 2007, 16, 532–537. [Google Scholar] [CrossRef]
- Bauskin, A.R.; Brown, D.A.; Kuffner, T.; Johnen, H.; Luo, X.W.; Hunter, M.; Breit, S.N. Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res. 2006, 66, 4983–4986. [Google Scholar] [CrossRef] [PubMed]
- Bansal, N.; Kumar, D.; Gupta, A.; Chandra, D.; Sankhwar, S.N.; Mandhani, A. Relevance of MIC-1 in the Era of PSA as a serum based predictor of prostate cancer: A critical evaluation. Sci. Rep. 2017, 7, 16824. [Google Scholar] [CrossRef] [PubMed]
- Karan, D.; Tawfik, O.; Dubey, S. Expression analysis of inflammasome sensors and implication of nlrp12 inflammasome in prostate cancer. Sci. Rep. 2017, 7, 4378. [Google Scholar] [CrossRef] [PubMed]
- Allaire, J.J. Rstudio: Integrated Development for R; Rstdio: Boston, MA, USA, 2019. [Google Scholar]
- Brown, D.A.; Lindmark, F.; Stattin, P.; Balter, K.; Adami, H.O.; Zheng, S.L.; Xu, J.; Isaacs, W.B.; Gronberg, H.; Breit, S.N.; et al. Macrophage inhibitory cytokine 1: A new prognostic marker in prostate cancer. Clin. Cancer Res. 2009, 15, 6658–6664. [Google Scholar] [CrossRef]
- Li, J.; Veltri, R.W.; Yuan, Z.; Christudass, C.S.; Mandecki, W. Macrophage inhibitory cytokine 1 biomarker serum immunoassay in combination with psa is a more specific diagnostic tool for detection of prostate cancer. PLoS ONE 2015, 10, e0122249. [Google Scholar] [CrossRef]
- Breit, S.N.; Johnen, H.; Cook, A.D.; Tsai, V.W.; Mohammad, M.G.; Kuffner, T.; Zhang, H.P.; Marquis, C.P.; Jiang, L.; Lockwood, G.; et al. The tgf-beta superfamily cytokine, mic-1/gdf15: A pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors 2011, 29, 187–195. [Google Scholar] [CrossRef]
- Fisher, O.M.; Levert-Mignon, A.J.; Lord, S.J.; Lee-Ng, K.K.; Botelho, N.K.; Falkenback, D.; Thomas, M.L.; Bobryshev, Y.V.; Whiteman, D.C.; Brown, D.A.; et al. Mic-1/gdf15 in barrett’s oesophagus and oesophageal adenocarcinoma. Br. J. Cancer 2015, 112, 1384–1391. [Google Scholar] [CrossRef]
- Iczkowski, K.A.; Kravtsov, O.; Sadasivan, S.; Palangmonthip, W.; Chen, Y.; Lucia, M.S.; Lambert, J.R.; Torkko, K.C.; Rybicki, B.A. Racial disparities in expression of gdf15 and nf-kb in prostate cancer and benign prostatic epithelium. Prostate 2020, in press. [Google Scholar]
- Shim, M.; Eling, T.E. Protein kinase c-dependent regulation of nag-1/placental bone morphogenic protein/mic-1 expression in lncap prostate carcinoma cells. J. Biol. Chem. 2005, 280, 18636–18642. [Google Scholar] [CrossRef]
- Domingo-Domenech, J.; Mellado, B.; Ferrer, B.; Truan, D.; Codony-Servat, J.; Sauleda, S.; Alcover, J.; Campo, E.; Gascon, P.; Rovira, A.; et al. Activation of nuclear factor-kappab in human prostate carcinogenesis and association to biochemical relapse. Br. J. Cancer 2005, 93, 1285–1294. [Google Scholar] [CrossRef]
- Ratnam, N.M.; Peterson, J.M.; Talbert, E.E.; Ladner, K.J.; Rajasekera, P.V.; Schmidt, C.R.; Dillhoff, M.E.; Swanson, B.J.; Haverick, E.; Kladney, R.D.; et al. Nf-kappab regulates gdf-15 to suppress macrophage surveillance during early tumor development. J. Clin. Investig. 2017, 127, 3796–3809. [Google Scholar] [CrossRef] [PubMed]
- de Lima, M.M.; Filho, S.S.J.; Tobias-Machado, M. Association between psa and age in macuxi ethnic population of the brazilian amazon forest region. Res. Rep. Urol. 2018, 10, 159–168. [Google Scholar] [CrossRef] [PubMed]
- Wischhusen, J.; Melero, I.; Fridman, W.H. Growth/differentiation factor-15 (gdf-15): From biomarker to novel targetable immune checkpoint. Front. Immunol. 2020, 11, 951. [Google Scholar] [CrossRef]
- Stejskal, D.; Karpisek, M.; Humenanska, V.; Lacnak, B.; Svestak, M. Macrophage-inhibitory cytokine-1 (mic-1) in differential diagnosis of dyspnea—A pilot study. Clin. Biochem. 2009, 42, 1347–1351. [Google Scholar] [CrossRef]
- Liu, Y.; Wang, X.; Wang, T.; Zhang, C.; Zhang, K.; Zang, R.; Zhi, X.; Zhang, W.; Sun, K. Macrophage inhibitory cytokine-1 (mic-1) as a biomarker for diagnosis and prognosis of stage i-ii non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 2016, 19, 207–215. [Google Scholar] [PubMed]
- Karan, D.; Holzbeierlein, J.; Thrasher, J.B. Macrophage inhibitory cytokine-1: Possible bridge molecule of inflammation and prostate cancer. Cancer Res. 2009, 69, 2–5. [Google Scholar] [CrossRef]
Clinical Characteristics | All Samples (n = 159) | African American | Caucasian | pc | |||
---|---|---|---|---|---|---|---|
Case (n = 50) | Control (n = 34) | Case (n = 55) | Control (n = 20) | ||||
PSA (ng/mL) a | 7.8 (4.7) | 8.6 (5.3) | — | 7.0 (4.0) | — | 0.09 | |
Age (years) a | 55.6 (14.0) | 59.9 (7.4) | 40.7 (19.0) | 62.0 (8.1) | 52.6 (10.7) | 0.02 | |
Gleason Score a | 6.7 (0.9) | 6.9 (0.7) | — | 6.5 (1.1) | — | 0.01 | |
Stage b | T1 | 2 (2.1) | 2 (4.0) | — | 0 (0) | — | 0.03 |
T1a | 1 (1.1) | 1 (2.0) | — | 0 (0) | — | ||
T1c | 6 (6.4) | 6 (12.0) | — | 0 (0) | — | ||
T2 | 1 (1.1) | 1 (2.0) | 0 (0) | ||||
pT2a | 12 (12.8) | 4 (8.0) | — | 8 (18.2) | — | ||
pT2b | 3 (3.2) | 2 (4.0) | — | 1 (2.3) | — | ||
pT2c | 62 (66.0) | 33 (66.0) | — | 29 (65.9) | — | ||
pT3a | 4 (4.3) | 1 (2.0) | — | 3 (6.8) | — | ||
pT3c | 2 (2.1) | 0 (0) | — | 2 (4.5) | — | ||
pT4a | 1 (1.1) | 0 (0) | — | 1 (2.3) | — | ||
Missing | 11 (10.5) | 0 (0) | 11 (20.0) |
Parameters | All Samples | African American | Caucasian | |||
---|---|---|---|---|---|---|
logSerum MIC-1 (units) | logUrine MIC-1 (units) | logSerum MIC-1 (units) | logUrine MIC-1 (units) | logSerum MIC-1 (units) | logUrine MIC-1 (units) | |
logSerum MIC-1 (units) | — | — | — | — | — | — |
logUrine MIC-1 (units) | r = 0.48 p = 0.02 n = 25 | — | r = 0.46 p = 0.19 n = 10 | — | r = 0.35 p = 0.2 n = 15 | — |
Age (years) | r = 0.35 p < 0.01 n = 105 | r = 0.12 p = 0.57 n = 25 | r = 0.16 p = 0.27 n = 50 | r = -0.12 p = 0.74 n = 10 | r = 0.67 p < 0.01 n = 55 | r = 0.41 p = 0.13 n = 15 |
PSA (units) | r = 0.19 p = 0.05 n = 105 | r = 0.16 p = 0.45 n = 25 | r = 0.04 p = 0.78 n = 50 | r = 0.37 p = 0.29 n = 10 | r = 0.26 p = 0.06 n = 55 | r = 0.01 p = 0.99 n = 15 |
Gleason Score | r = 0.25 p = 0.01 n = 105 | r = 0.15 p = 0.46 n = 25 | r = 0.11 p = 0.47 n = 50 | r = 0.36 p = 0.31 n = 10 | r = 0.22 p = 0.11 n = 55 | r = −0.15 p = 0.59 n = 15 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Karan, D.; Wick, J.; Dubey, S.; Tawfik, O.; Van Veldhuizen, P. Circulatory MIC-1 as a Determinant of Prostate Cancer Racial Disparity. Cancers 2020, 12, 3033. https://doi.org/10.3390/cancers12103033
Karan D, Wick J, Dubey S, Tawfik O, Van Veldhuizen P. Circulatory MIC-1 as a Determinant of Prostate Cancer Racial Disparity. Cancers. 2020; 12(10):3033. https://doi.org/10.3390/cancers12103033
Chicago/Turabian StyleKaran, Dev, Jo Wick, Seema Dubey, Ossama Tawfik, and Peter Van Veldhuizen. 2020. "Circulatory MIC-1 as a Determinant of Prostate Cancer Racial Disparity" Cancers 12, no. 10: 3033. https://doi.org/10.3390/cancers12103033
APA StyleKaran, D., Wick, J., Dubey, S., Tawfik, O., & Van Veldhuizen, P. (2020). Circulatory MIC-1 as a Determinant of Prostate Cancer Racial Disparity. Cancers, 12(10), 3033. https://doi.org/10.3390/cancers12103033