Novel Blood Indicators of Progression and Prognosis in Renal Cell Carcinoma: Red Cell Distribution Width-to-Lymphocyte Ratio and Albumin-to-Fibrinogen Ratio

Chenjun Ma, Quan Liu, Chengyang Li, Jiwen Cheng, Deyun Liu, Zhanbin Yang, Haibiao Yan, Bo Wu, Yongxian Wu, Jiawen Zhao, Chenjun Ma, Quan Liu, Chengyang Li, Jiwen Cheng, Deyun Liu, Zhanbin Yang, Haibiao Yan, Bo Wu, Yongxian Wu, Jiawen Zhao

Abstract

Objective: To evaluate the value of preoperative red cell distribution width-to-lymphocyte ratio (RLR) and albumin-to-fibrinogen ratio (AFR) to the prognosis of patients after renal cell carcinoma (RCC).

Methods: From 2012 to 2016, a total of 273 RCC patients underwent radical nephrectomy or partial nephrectomy. This study retrospectively analyzed this group of patients. X-tile software was used to determine the optimal values of RLR and AFR in the peripheral blood. The nomogram constructed with independent factors was used to predict the survival outcome of the patients after RCC.

Results: The RLR of the RCC group was higher than that of the normal control group (P=0.002), whereas the AFR of the RCC group was lower than that of the normal control group (P < 0.001). RLR and AFR are related to tumour type and tumour-node-metastasis (TNM) stage (P < 0.05 for all). Cox regression analysis showed that the independent prognostic factors affecting overall survival and disease-free survival in the RCC group were symptom, tumour type, TNM stage, Fuhrman grade, RLR, and AFR (P < 0.05 for all). The nomogram constructed by multiple factors has better predictive power for patients after RCC.

Conclusion: Preoperative RLR and AFR can serve as potential biomarkers to predict the prognosis of postoperative RCC patients and improve the predictability of patient recurrence and survival.

Conflict of interest statement

The authors declared that there are no conflicts of interest regarding the publication of this article.

Copyright © 2020 Chenjun Ma et al.

Figures

Figure 1
Figure 1
The 5-year OS (AF) and DFS (G-L) were x-tile analyzed using patient data to determine the optimal cutoff value for blood RLR and AFR. (a, d, g, j) The data are represented by the panel graph in different colors to indicate possible cutoff values. The best cutting point (8.8 and 9.0, respectively) is determined by the black circle on the x-tile image and shown in the histogram in the middle. (b, e, h, k) The histograms of the distribution of the number of people in RLR and AFR, and the kaplanMeier curves of OS (c, f) and DFS (i, l) show the difference in survival of different groups of RLR and AFR.
Figure 2
Figure 2
Blood cell counts from healthy people and patients with RCC. (a, b) There was no significant difference in age and gender between NVs and patients with RCC (both P > 0.05). (c) Correlations of RLR with AFR in RCC patients. The lymphocyte counts (d), albumin (g), and albumin-to-fibrinogen ratio (i) in patients with RCC were significantly lower than those in healthy people. The red cell distribution width (e), RDW-to-lymphocyte ratio (f), and fibrinogen (h) in RCC patients were significantly higher than those in healthy people.
Figure 3
Figure 3
Forest plot showing OS (a) and DFS (b) according to subgroup effects. HR, hazard ratio; CI, confidence interval.
Figure 4
Figure 4
Cox regression forest plot of circulating inflammatory biomarkers showing OS (a) and DFS (b) in each subgroup. HR, hazard ratio; CI, confidence interval.
Figure 5
Figure 5
Nomogram to estimate the probability of OS (a) and DFS (b) at 3 and 5 years.
Figure 6
Figure 6
Calibration curves of the nomogram for 3-year OS (a), 5-year OS, (b) 3-year DFS, and (c) and 5-year DFS (d).
Figure 7
Figure 7
C index forest plots of different models. C index for predicting the survival probability of (a) OS in 5 years and (b) DFS in 5 years. Model: RLR + AFR + symptom + tumour type + TNM + Fuhrman grade; Model 1: RLR + symptom + tumour type + TNM + Fuhrman grade; Model 2: AFR + symptom + tumour type + TNM + Fuhrman grade; Model 3: symptom + tumour type + TNM + Fuhrman grade; Model 4: TNM + Fuhrman grade; Model 5: symptom + tumor size; Model 6: TNM.

References

    1. Siegel R. L., Miller K. D., Jemal A. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians. 2020;70(1):7–30. doi: 10.3322/caac.21590.
    1. Leibovich B. C., Blute M. L., Cheville J. C., et al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma. Cancer. 2003;97(7):1663–1671. doi: 10.1002/cncr.11234.
    1. Shao Y., Xiong S., Sun G., et al. Prognostic analysis of postoperative clinically nonmetastatic renal cell carcinoma. Cancer Medicine. 2020;9(3):959–970. doi: 10.1002/cam4.2775.
    1. Zisman A., Pantuck A. J., Dorey F., et al. Mathematical model to predict individual survival for patients with renal cell carcinoma. Journal of Clinical Oncology. 2002;20(5):1368–1374. doi: 10.1200/jco.2002.20.5.1368.
    1. Frank I., Blute M. L., Cheville J. C., Lohse C. M., Weaver A. L., Zincke H. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. Journal of Urology. 2002;168(6):2395–2400. doi: 10.1016/s0022-5347(05)64153-5.
    1. Fukuokaya W., Kimura T., Onuma H., et al. Red cell distribution width predicts prostate-specific antigen response and survival of patients with castration-resistant prostate cancer treated with androgen receptor axis-targeted agents. Clinical Genitourinary Cancer. 2019;17(3):223–230. doi: 10.1016/j.clgc.2019.04.010.
    1. Fukuokaya W., Kimura T., Miki J., et al. Red cell distribution width predicts time to recurrence in patients with primary non-muscle-invasive bladder cancer and improves the accuracy of the EORTC scoring system. Urologic Oncology: Seminars and Original Investigations. 2020;38(7):e15–e28. doi: 10.1016/j.urolonc.2020.01.016.
    1. Zhao J., Huang W., Wu Y., et al. Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis. Cancer Cell International. 2020;20:p. 15. doi: 10.1186/s12935-020-1094-5.
    1. Zhang Y., Xiao G. Prognostic significance of the ratio of fibrinogen and albumin in human malignancies: a meta-analysis. Cancer Management and Research. 2019;11:3381–3393. doi: 10.2147/cmar.s198419.
    1. Xu W.-Y., Zhang H.-H., Xiong J.-P., et al. Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients. World Journal of Gastroenterology. 2018;24(29):3281–3292. doi: 10.3748/wjg.v24.i29.3281.
    1. Zhao J., Zhao M., Jin B., et al. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen. Bmc Cancer. 2012;12(1) doi: 10.1186/1471-2407-12-330.
    1. Pichler M., Hutterer G. C., Stojakovic T., Mannweiler S., Pummer K., Zigeuner R. High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific, metastasis-free, as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients. British Journal of Cancer. 2013;109(5):1123–1129. doi: 10.1038/bjc.2013.443.
    1. Edge S. B., Compton C. C. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of Surgical Oncology. 2010;17(6):1471–1474. doi: 10.1245/s10434-010-0985-4.
    1. Erdoğan F., Demirel A., Polat O. Prognostic significance of morphologic parameters in renal cell carcinoma. International Journal of Clinical Practice. 2004;58(4):333–336. doi: 10.1111/j.1368-5031.2004.00008.x.
    1. Ljungberg B., Albiges L., Abu-Ghanem Y., et al. European association of urology guidelines on renal cell carcinoma: the 2019 update. European Urology. 2019;75(5):799–810. doi: 10.1016/j.eururo.2019.02.011.
    1. Patard J.-J., Leray E., Cindolo L., et al. Multi-institutional validation of a symptom based classification for renal cell carcinoma. Journal of Urology. 2004;172(3):858–862. doi: 10.1097/01.ju.0000135837.64840.55.
    1. Chechlinska M., Kowalewska M., Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nature Reviews Cancer. 2010;10(1):2–3. doi: 10.1038/nrc2782.
    1. Spano D., Zollo M. Tumor microenvironment: a main actor in the metastasis process. Clinical and Experimental Metastasis. 2012;29(4):381–395. doi: 10.1007/s10585-012-9457-5.
    1. De Gonzalo-Calvo D., De Luxán-Delgado B., Rodríguez-González S., et al. Interleukin 6, soluble tumor necrosis factor receptor I and red blood cell distribution width as biological markers of functional dependence in an elderly population: a translational approach. Cytokine. 2012;58(2):0–198. doi: 10.1016/j.cyto.2012.01.005.
    1. Lippi G., Targher G., Montagnana M., Salvagno G. L., Zoppini G., Guidi G. C. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Archives of Pathology and Laboratory Medicine. 2009;133(4):628–632.
    1. Hu L., Li M., Ding Y., et al. Prognostic value of RDW in cancers: a systematic review and meta-analysis. Oncotarget. 2017;8(9):16027–16035. doi: 10.18632/oncotarget.13784.
    1. Grivennikov S. I., Greten F. R., Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–899. doi: 10.1016/j.cell.2010.01.025.
    1. Ownby H. E., Roi L. D., Isenberg R. R., Brennan M. J. Peripheral lymphocyte and eosinophil counts as indicators of prognosis in primary breast cancer. Cancer. 1983;52(1):126–130.
    1. Margetts J., Ogle L. F., Chan S. L., et al. Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma? British Journal of Cancer. 2017;118(2) doi: 10.1038/bjc.2017.386.bjc2017386
    1. Chen L., Kong X., Yan C., Fang Y., Wang J. The research progress on the prognostic value of the common hematological parameters in peripheral venous blood in breast cancer. Onco Targets and Therapy. 2020;13:1397–1412. doi: 10.2147/ott.s227171.
    1. Biscetti F., Flex A., Pecorini G., et al. The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor. Clinical and Experimental Immunology. 2016;184(1):62–72. doi: 10.1111/cei.12758.
    1. Adams G. N., Rosenfeldt L., Frederick M., et al. Colon cancer growth and dissemination relies upon thrombin, stromal PAR-1, and fibrinogen. Cancer Research. 2015;75(19) doi: 10.1158/0008-5472.can-15-0964.
    1. McMillan D. C. Systemic inflammation, nutritional status and survival in patients with cancer. Current Opinion in Clinical Nutrition and Metabolic Care. 2009;12(3):223–226.
    1. Seaton K. Albumin concentration controls cancer. Journal of the National Medical Association. 2001;93(12):490–493.
    1. Sun D. W., An L., Lv G. Y. Albumin-fibrinogen ratio and fibrinogen-prealbumin ratio as promising prognostic markers for cancers: an updated meta-analysis. World Journal of Surgical Oncology. 2020;18(1):p. 9. doi: 10.1186/s12957-020-1786-2.
    1. Hutterer G. C., Patard J. J., Jeldres C., et al. Patients with distant metastases from renal cell carcinoma can be accurately identified: external validation of a new nomogram. Bju International. 2008;101(1):39–43. doi: 10.1111/j.1464-410X.2007.07170.x.
    1. Volpe A., Patard J. J. Prognostic factors in renal cell carcinoma. World Journal of Urology. 2010;28(3):319–327. doi: 10.1007/s00345-010-0540-8.

Source: PubMed

Подписаться