Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 24;9(31):21861-21875.
doi: 10.18632/oncotarget.25076.

Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome

Stefan Janik  1   2 , Thomas Raunegger  1   2 , Philipp Hacker  1   2 , Bahil Ghanim  1 , Elisa Einwallner  3 , Leonhard Müllauer  4 , Ana-Iris Schiefer  4 , Julia Moser  5 , Walter Klepetko  1 , Hendrik Jan Ankersmit  1   2   6 , Bernhard Moser  1
Affiliations

Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome

Stefan Janik et al. Oncotarget. .

Abstract

Background: Peripheral blood-derived inflammation-based markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Fibrinogen have been identified as prognostic markers in various solid malignancies. Here we aimed to investigate the prognostic and diagnostic impact of NLR, PLR, and Fibrinogen in patients with thymic epithelial tumors (TETs).

Results: Pretreatment Fibrinogen serum concentrations, NLRs and PLRs were highest in patients with TCs and advanced tumor stages. High pretreatment Fibrinogen serum concentration (≥452.5 mg/dL) was significantly associated with worse cause specific survival (CSS; p = 0.001) and freedom from recurrence (FFR; p = 0.043), high NLR (≥4.0) with worse FFR (p = 0.008), and high PLR (≥136.5) with worse CSS (p = 0.032). Longitudinal analysis revealed that compared to patients without tumor recurrence, patients with tumor recurrence had significantly higher NLR (11.8 ± 4.0 vs. 4.70 ± 0.5; p = 0.001) and PLR (410.8 ± 149.1 vs. 228.3 ± 23.7; p = 0.031).

Conclusion: Overall, Fibrinogen serum concentrations, NLRs, and PLRs were associated with higher tumor stage, more aggressive tumor behavior, recurrence, and worse outcome. Prospective multicenter studies of the diagnostic and prognostic potential of Fibrinogen, NLR, and PLR are warranted.

Methods: This retrospective analysis included 122 patients with TETs who underwent surgical resection between 1999-2015. Fibrinogen serum concentrations, NLRs, and PLRs were measured in patients preoperatively, postoperatively, and later during follow-up. These markers were analyzed for association with several clinical variables, including tumor stage, tumor subtype, FFR, and CSS and to evaluate their prognostic and diagnostic impact for detecting tumor recurrence.

Keywords: NLR; fibrinogen; thymic carcinoma; thymic epithelial tumors; thymoma.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Fibrinogen and absolute lymphocyte numbers according to clinical Masaoka-Koga tumor stage
Fibrinogen serum concentrations gradually increased with invasiveness level (A). Peripheral blood absolute lymphocyte numbers gradually decreased with tumor stage (B).
Figure 2
Figure 2. Kaplan–Meier survival curves for Fibrinogen, NLR, and PLR
Graphs show the associations between Fibrinogen and FFR (A) and CSS (B), between NLR and FFR (C) and CSS (D) , and between PLR and FFR (E) and CSS (F). The cut-off values used to dichotomize patients into low and high subgroups were 452.5 mg/dL for Fibrinogen, 4.0 for NLR, and 136.5 for PLR. NLR, Neutrophil-to-Lymphocyte Ratio; PLR, Platelet-to-Lymphocyte Ratio.
Figure 3
Figure 3. Longitudinal analysis of Fibrinogen, NLR, and PLR
Plots illustrate how surgical tumor resection and recurrence were related to Fibrinogen, NLR, and PLR in thymomas (A, D, G) and thymic carcinomas (B, E, H), as well as the longitudinal courses of Fibrinogen, NLR, and PLR according to tumor recurrence among TETs (C, F, I). NLR, Neutrophil-to-Lymphocyte Ratio; PLR, Platelet-to-Lymphocyte Ratio; mo, months; TETs, thymic epithelial tumors.
Figure 4
Figure 4. The accuracy of predicting tumor recurrence in patients with TETs based on NLR and PLR values during oncologic follow-up
Receiver operating characteristic (ROC) curves for the use of NLR (A) and PLR (B) to predict tumor recurrence during oncologic follow-up showed area under the curve (AUC) values of 0.819 (p = 0.024) and 0.787 (p = 0.042), respectively. The dotted lines indicate the highest Youden Indices for NLR (Youden Index = 0.574; sensitivity = 0.800; specificity = 0.226; cut-off at 6.6) and PLR (Youden Index = 0.581; sensitivity = 1.000; specificity = 0.419; cut-off at 202.5). NLR, Neutrophil-to-Lymphocyte Ratio; PLR, Platelet-to-Lymphocyte Ratio.
Figure 5
Figure 5. Fibrinogen expression in B2/B3 thymoma
Staining of a B2/B3 thymoma (B3 part) with Hematoxylin-Eosin (A) and for Fibrinogen (B) and CD45 (C) expression. 100× magnification. Asterisks indicate neoplastic thymic epithelial cells. Arrows indicate cells of the hematopoietic lineage. Fibrinogen expression is absent from tumor cells and lymphocytes. Lymphocytes exhibit CD45 expression.
See this image and copyright information in PMC

References

    1. Marx A, Chan JK, Coindre JM, Detterbeck F, Girard N, Harris NL, Jaffe ES, Kurrer MO, Marom EM, Moreira AL, Mukai K, Orazi A, Ströbel P. The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes. J Thorac Oncol. 2015;10:1383–95. - PMC - PubMed
    1. Detterbeck FC, Parsons AM. Management of stage I and II thymoma. Thorac Surg Clin. 2011;21:59–6. - PubMed
    1. Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, Kondo K, Marino M, Marom EM, Nicholson AG, et al. Staging and Prognostic Factors Committee; Advisory Boards. The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9:S88–96. - PubMed
    1. Detterbeck FC, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Frazier AA, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, et al. Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014;9:S65–72. - PubMed
    1. Kondo K, Van Schil P, Detterbeck FC, Okumura M, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Giaccone G, Huang J, Kim J, et al. Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposals for the N and M components for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014;9:S81–7. - PubMed

LinkOut - more resources