儿童神经母细胞瘤切除术后的生存预测因素
Predictors of Survival after Resection of Children with Neuroblastoma
DOI: 10.12677/ACM.2022.1291190, PDF,   
作者: 姬 铭, 张 鹏, 朱 谦, 郝希伟*：青岛大学附属医院，山东 青岛
关键词: 神经母细胞瘤；手术；儿童；预后；Neuroblastoma； Surgery； Children； Prognosis
摘要: 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。
Abstract: 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.
文章引用：姬铭, 张鹏, 朱谦, 郝希伟. 儿童神经母细胞瘤切除术后的生存预测因素[J]. 临床医学进展, 2022, 12(9): 8256-8265. https://doi.org/10.12677/ACM.2022.1291190

参考文献

[1] Irwin, M.S. and Park, J.R. (2015) Neuroblastoma: Paradigm for Precision Medicine. Pediatric Clinics of North America, 62, 225-256. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] 
[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. [Google Scholar] [CrossRef] [PubMed]
[5] Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674. [Google Scholar] [CrossRef] [PubMed]
[6] Mantovani, A., Allavena, P., Sica, A. and Balkwill, F. (2008) Can-cer-Related Inflammation. Nature, 454, 436-444. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] 
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] 
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[22] Brodeur, G.M. and Bagatell, R. (2014) Mechanisms of Neuroblastoma Regression. Nature Reviews Clinical Oncology, 11, 704-713. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[29] Powell, D.R. and Huttenlocher, A. (2016) Neutrophils in the Tu-mor Microenvironment. Trends in Immunology, 37, 41-52. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] 
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] [PubMed]
[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. [Google Scholar] [CrossRef] 
[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. [Google Scholar] [CrossRef] [PubMed]

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