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儿童神经母细胞瘤切除术后的生存预测因素
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Abstract:
目的：探究术前中性粒细胞与淋巴细胞的比值(neutrophil to lymphocyte ratio, NLR)和血清C反应蛋白(c-reactive protein, CRP)与白蛋白(albumin, ALB)的比值(CRP/ALB ratio, CAR)对儿童神经母细胞瘤切除术后预后的预测价值。方法：利用受试者工作特征(ROC)曲线用于确定连续变量CAR与NLR的最佳截断值。并将患者分为三组：低NLR与低CAR被定义为NLR-CAR 0，高NLR与高CAR被定义为NLR-CAR 2，低NLR与高CAR或者高NLR与低CAR定义为NLR-CAR 1。Kaplan-Meier方法和Log-rank方法用于生存分析。采用单变量与多变量Cox比例风险回归来确定NB患者预后的独立因素。结果：根据ROC曲线，NLR的最佳截断值为2.49，CAR的最佳截断值为0.035。Kaplan-Meier方法显示，高NLR (>2.49)、高CAR (>0.035)以及NLR-CAR 2具有较差的总体生存期(P < 0.01)。单因素及多因素Cox回归分析显示，年龄(>18个月)、INSS分期(III-IV)以及NLR-CAR 2 (高NLR和高CAR)是NB患者预后的独立的危险因素(P < 0.05)。结论：NLR-CAR 2 (高NLR和高CAR)是NB患儿预后有价值的生物标志物。
OBJECTIVE: To investigate the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) and serum C-reactive protein to albumin ratio (CAR) on the prognosis after resection of neuroblas-toma in children. METHODS: Subject operating characteristic (ROC) curves were used to determine the optimal cut-off values for the continuous variable CAR versus NLR. And patients were divided into three groups: low NLR with low CAR was defined as NLR-CAR 0, high NLR with high CAR was de-fined as NLR-CAR 2, and low NLR with high CAR or high NLR with low CAR was defined as NLR-CAR 1. Kaplan-Meier method and Log-rank method were used for survival analysis. Univariate versus mul-tivariate Cox proportional risk regression was used to determine independent factors of prognosis in NB patients. RESULTS: According to the ROC curve, the optimal cut-off value for NLR was 2.49 and for CAR was 0.035. Kaplan-Meier method showed that high NLR (>2.49), high CAR (>0.035) and NLR-CAR 2 had poorer overall survival (P < 0.01). Univariate and multifactorial Cox regression analysis showed that age (>18 months), INSS stage (III-IV), and NLR-CAR 2 (high NLR and high CAR) were independent risk factors for the prognosis of NB patients (P < 0.05). CONCLUSION: NLR-CAR 2 (high NLR and high CAR) is a valuable biomarker for the prognosis of children with NB.
| [1] | Irwin, M.S. and Park, J.R. (2015) Neuroblastoma: Paradigm for Precision Medicine. Pediatric Clinics of North America, 62, 225-256. https://doi.org/10.1016/j.pcl.2014.09.015 |
| [2] | Theissen, J., Oberthuer, A., Hombach, A., et al. (2014) Chromosome Gain and Unaltered Profiles in High Resolution Array-CGH Are Prognostically Informative in Neuroblas-toma. Genes Chromosomes Cancer, 53, 639-649.
https://doi.org/10.1002/gcc.22174 |
| [3] | Liu, H.Y., Liu, C.X., Han, B., et al. (2012) AEG-1 Is Associated with Clinical Outcome in Neuroblastoma Patients. Cancer Biomark, 11, 115-121. https://doi.org/10.3233/CBM-2012-0268 |
| [4] | Van Wezel, E.M., Decarolis, B., Stutterheim, J., et al. (2016) Neuro-blastoma Messenger RNA Is Frequently Detected in Bone Marrow at Diagnosis of Localised Neuroblastoma Patients. European Journal of Cancer, 54, 149-158.
https://doi.org/10.1016/j.ejca.2015.11.007 |
| [5] | Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.
https://doi.org/10.1016/j.cell.2011.02.013 |
| [6] | Mantovani, A., Allavena, P., Sica, A. and Balkwill, F. (2008) Can-cer-Related Inflammation. Nature, 454, 436-444.
https://doi.org/10.1038/nature07205 |
| [7] | Larsson, K., Kock, A., Idborg, H., et al. (2015) COX/mPGES-1/PGE2 Pathway Depicts an Inflammatory-Dependent High-Risk Neuroblastoma Subset. Proceedings of the National Academy of Sciences of the United States of America, 112, 8070-8075. https://doi.org/10.1073/pnas.1424355112 |
| [8] | Asgharzadeh, S., Salo, J.A., Ji, L., et al. (2012) Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma. Journal of Clinical Oncology, 30, 3525-3532. https://doi.org/10.1200/JCO.2011.40.9169 |
| [9] | Carlson, L.M., Rasmuson, A., Idborg, H., et al. (2013) Low-Dose Aspirin Delays an Inflammatory Tumor Progression in Vivo in a Transgenic Mouse Model of Neuroblastoma. Carcino-genesis, 34, 1081-1088.
https://doi.org/10.1093/carcin/bgt009 |
| [10] | Zhang, Z., Zhou, Y., Hu, K. and Huang, Y. (2020) Investigating Effects of Preoperative Inflammatory Biomarkers on Predicting Survival Outcomes of Intrahepatic Cholangiocarcinoma after Curative Resection. World Journal of Surgical Oncology, 18, 272. https://doi.org/10.1186/s12957-020-02053-w |
| [11] | Li, F., Zhang, W., Hu, H., et al. (2019) Diagnostic Value of Procalcitonin, C-Reactive Protein and Lactate Dehydrogenase in Paediatric Malignant Solid Tumour Concurrent with In-fection and Tumour Progression. Scientific Reports, 9, Article No. 5903. https://doi.org/10.1038/s41598-019-42264-0 |
| [12] | Guo, F., Ru, Q., Zhang, J., et al. (2017) Inflammation Factors in Hepatoblastoma and Their Clinical Significance as Diagnostic and Prognostic Biomarkers. Journal of Pediatric Surgery, 52, 1496-1502.
https://doi.org/10.1016/j.jpedsurg.2017.01.059 |
| [13] | Russo, A., Russano, M., Franchina, T., et al. (2020) Neutro-phil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study. Advances in Therapy, 37, 1145-1155. https://doi.org/10.1007/s12325-020-01229-w |
| [14] | Wang, D., Bai, N., Hu, X., et al. (2019) Preoperative Inflam-matory Markers of NLR and PLR as Indicators of Poor Prognosis in Resectable HCC. PeerJ, 7, e7132. https://doi.org/10.7717/peerj.7132 |
| [15] | Gao, Y., Wang, W.J., Zhi, Q., et al. (2017) Neutrophil/Lymphocyte Ratio Is a More Sensitive Systemic Inflammatory Response Biomarker than Platelet/Lymphocyte Ratio in the Prognosis Evalua-tion of Unresectable Pancreatic Cancer. Oncotarget, 8, 88835-88844. https://doi.org/10.18632/oncotarget.21340 |
| [16] | Yin, X., Wu, L., Yang, H. and Yang, H. (2019) Prognostic Signif-icance of Neutrophil-Lymphocyte Ratio (NLR) in Patients with Ovarian Cancer: A Systematic Review and Me-ta-Analysis. Medicine (Baltimore), 98, e17475.
https://doi.org/10.1097/MD.0000000000017475 |
| [17] | Du, S., Fang, Z., Ye, L., et al. (2021) Pretreatment Neutro-phil-to-Lymphocyte Ratio Predicts the Benefit of Gastric Cancer Patients with Systemic Therapy. Aging (Albany NY), 13, 17638-17654. https://doi.org/10.18632/aging.203256 |
| [18] | Huang, Z.Z., Wen, W., Hua, X., et al. (2021) Estab-lishment and Validation of Nomogram Based on Combination of Pretreatment C-Reactive Protein/Albumin Ratio-EBV DNA Grade in Nasopharyngeal Carcinoma Patients Who Received Concurrent Chemoradiotherapy. Frontiers in Oncol-ogy, 11, Article ID: 583283.
https://doi.org/10.3389/fonc.2021.583283 |
| [19] | Solano-Aguilar, G.I., Lakshman, S., Jang, S., et al. (2018) The Ef-fect of Feeding Cocoa Powder and Lactobacillus rhamnosus on the Composition and Function of Pig Intestinal Micro-biome. Current Developments in Nutrition, 2, nzy011.
https://doi.org/10.1093/cdn/nzy011 |
| [20] | Liu, X., Sun, X., Liu, J., et al. (2015) Preoperative C-Reactive Pro-tein/Albumin Ratio Predicts Prognosis of Patients after Curative Resection for Gastric Cancer. Translational Oncology, 8, 339-345.
https://doi.org/10.1016/j.tranon.2015.06.006 |
| [21] | Kinoshita, A., Onoda, H., Imai, N., et al. (2015) The C-Reactive Protein/Albumin Ratio, a Novel Inflammation-Based Prognostic Score, Predicts Outcomes in Patients with Hepatocellular Carcinoma. Annals of Surgical Oncology, 22, 803-810. https://doi.org/10.1245/s10434-014-4048-0 |
| [22] | Brodeur, G.M. and Bagatell, R. (2014) Mechanisms of Neuroblastoma Regression. Nature Reviews Clinical Oncology, 11, 704-713. https://doi.org/10.1038/nrclinonc.2014.168 |
| [23] | Kohler, J.A., Rubie, H., Castel, V., et al. (2013) Treat-ment of Children over the Age of One Year with Unresectable Localised Neuroblastoma without MYCN Amplification: Results of the SIOPEN Study. European Journal of Cancer, 49, 3671-3679. https://doi.org/10.1016/j.ejca.2013.07.002 |
| [24] | Borriello, L., Seeger, R.C., Asgharzadeh, S. and DeClerck, Y.A. (2016) More than the Genes, the Tumor Microenvironment in Neuroblastoma. Cancer Letters, 380, 304-314. https://doi.org/10.1016/j.canlet.2015.11.017 |
| [25] | Lin, N., Li, J., Ke, Q., et al. (2020) Clinical Significance of C-Reactive Protein to Albumin Ratio in Patients with Hepatocellular Carcinoma: A Meta-Analysis. Disease Markers, 2020, Article ID: 4867974.
https://doi.org/10.1155/2020/4867974 |
| [26] | Fridlender, Z.G., Albelda, S.M. and Granot, Z. (2015) Promoting Me-tastasis: Neutrophils and T Cells Join Forces. Cell Research, 25, 765-766. https://doi.org/10.1038/cr.2015.62 |
| [27] | Cools-Lartigue, J., Spicer, J., Najmeh, S. and Ferri, L. (2014) Neutrophil Extracellular Traps in Cancer Progression. Cellular and Molecular Life Sciences, 71, 4179-4194. https://doi.org/10.1007/s00018-014-1683-3 |
| [28] | Nayak, A., McDowell, D.T., Kellie, S.J. and Karpelowsky, J. (2017) Elevated Preoperative Neutrophil-Lymphocyte Ratio Is Predictive of a Poorer Prognosis for Pediatric Patients with Solid Tumors. Annals of Surgical Oncology, 24, 3456-3462. https://doi.org/10.1245/s10434-017-6006-0 |
| [29] | Powell, D.R. and Huttenlocher, A. (2016) Neutrophils in the Tu-mor Microenvironment. Trends in Immunology, 37, 41-52. https://doi.org/10.1016/j.it.2015.11.008 |
| [30] | Yoshikawa, T., Saito, H., Osaki, T., et al. (2008) Elevated Fas Ex-pression Is Related to Increased Apoptosis of Circulating CD8+ T Cell in Patients with Gastric Cancer. Journal of Sur-gical Research, 148, 143-151.
https://doi.org/10.1016/j.jss.2007.07.011 |
| [31] | Allin, K.H. and Nordestgaard, B.G. (2011) Elevated C-Reactive Protein in the Diagnosis, Prognosis, and Cause of Cancer. Critical Reviews in Clinical Laboratory Sciences, 48, 155-170. https://doi.org/10.3109/10408363.2011.599831 |
| [32] | Nazha, B., Moussaly, E., Zaarour, M., et al. (2015) Hypoal-buminemia in Colorectal Cancer Prognosis: Nutritional Marker or Inflammatory Surrogate? World Journal of Gastroin-testinal Surgery, 7, 370-377.
https://doi.org/10.4240/wjgs.v7.i12.370 |
| [33] | Yang, H., Wang, K., Liang, Z., et al. (2020) Prognostic Role of Pre-Treatment Serum Albumin in Patients with Nasopharyngeal Carcinoma: A Meta-Analysis and Systematic Review. Clinical Otolaryngology, 45, 167-176.
https://doi.org/10.1111/coa.13454 |
| [34] | Deng, T.B., Zhang, J., Zhou, Y.Z. and Li, W.M. (2018) The Prognostic Value of C-Reactive Protein to Albumin Ratio in Patients with Lung Cancer. Medicine (Baltimore), 97, e13505. https://doi.org/10.1097/MD.0000000000013505 |
| [35] | Fan, Y., Xiang, S., Dai, Z., et al. (2019) Prognostic Signifi-cance of C-Reactive Protein to Albumin Ratio in Colorectal Cancer Patients: A Meta-Analysis. International Journal of Colorectal Disease, 34, 1105-1111.
https://doi.org/10.1007/s00384-019-03299-x |
| [36] | Wu, J., Tan, W., Chen, L., et al. (2018) Clinicopathologic and Prognostic Significance of C-Reactive Protein/Albumin Ratio in Patients with Solid Tumors: An Updated Systemic Re-view and Meta-Analysis. Oncotarget, 9, 13934-13947.
https://doi.org/10.18632/oncotarget.24172 |
| [37] | Zheng, C., Liu, S., Feng, J. and Zhao, X. (2020) Prognostic Value of Inflammation Biomarkers for Survival of Patients with Neuroblastoma. Cancer Management and Research, 12, 2415-2425. https://doi.org/10.2147/CMAR.S245622 |
| [38] | Chen, Y.Y., Zhang, J.H., Zhang, W., et al. (2017) C-Reactive Protein/Albumin Ratio as a Novel Inflammation-Based Prognostic Index for Predicting Outcomes of Patients with Colorectal Cancer. Journal of Southern Medical University, 37, 622-627. |
| [39] | Al-Shaiba, R., McMillan, D.C., An-gerson, W.J., et al. (2004) The Relationship between Hypoalbuminaemia, Tumour Volume and the Systemic Inflamma-tory Response in Patients with Colorectal Liver Metastases. British Journal of Cancer, 91, 205-207. https://doi.org/10.1038/sj.bjc.6601886 |
