Skip to main content
Download PDF

Prognostic role of an inflammation scoring system in radical resection of oral squamous cell carcinoma

BMC Oral Health volume 22, Article number: 226 (2022) Cite this article

Abstract

Background

Inflammatory markers can influence the postoperative prognosis and outcome of malignant tumors. However, the role of inflammatory factors in oral squamous cell carcinoma (OSCC) are still debatable. The primary objective of this investigation was to detect the preoperative blood fibrinogen and neutrophil–lymphocyte ratio (NLR) in OSCC patients and to determine the predictive validity of F-NLR (combined fibrinogen and NLR score).

Methods

A total of 365 patients with oral cancer after surgery were separated into three classes: F-NLR of 2, with hyperfibrinogenemia (> 250 mg/dL) and high NLR (> 3.2); F-NLR of 1, with only one higher index; and F-NLR of 0, with no higher indices. Univariate and multivariate analyses were used to identify risk factors for the demographic and clinical characteristics of patients in the three F-NLR groups. Kaplan–Meier survival analysis was used to assess the prognosis.

Results

Preoperative F-NLR showed a relatively better predictive role in oral cancer prognosis than fibrinogen and NLR alone. Multivariate analysis revealed that F-NLR has the potential to be an independent predictor for OSCC cancer-specific survival (P < 0.001). Patients with high scores had a relatively poorer prognosis than those with low scores (P < 0.001).

Conclusions

Our findings indicate that blood F-NLR may serve as an independent prognostic factor in OSCC patients.

Peer Review reports

Background

The most common cancer in the oral cavity is oral squamous cell carcinoma (OSCC) [1]. OSCC is a highly metastatic tumor, and even patients in early stages have a high rate of recurrence and metastasis. Surgery, radiation, targeted therapy, and chemotherapy are the predominant treatment options for oral cancer, depending on the kind and severity of the disease [2]. Although there have been steady advancements in treatment, OSCC has a poor prognosis when compared to other head and neck cancers. The most likely reason is a combination of variables, including tumor depth, local invasion, nodal involvement, and perineural invasion [3]. Regretfully, these parameters can only be determined after surgical excision and histological investigation. Accordingly, it is critical to determine whether blood indicators can predict OSCC prognosis during the initial clinical evaluation.

Multiple studies have been conducted for years to correlate blood inflammatory factors to predict survival in patients with OSCC. Cancer cell adhesion is facilitated by systemic inflammation, which is signaled by the increase in circulating neutrophils at the front line of defense [4,5,6]. An important feature of cancer is the ability to evade killing by the immune system [7]. Studies have shown that tumor-infiltrating lymphocytes (TILs) play a key role in tumor progression in the tumor immune microenvironment, including that of OSCC [8, 9]. Multiple studies have confirmed that elevated levels of TILs are associated with good prognosis in OSCC [10, 11]. Lymphocytes, particularly cytotoxic lymphocytes, influence cancer progression and cancer treatment by eliminating tumor cells [12, 13]. The available evidence suggests that increased pretreatment neutrophil and lymphocyte numbers are correlated with a poor cancer outcome [14,15,16].

Fibrinogen is a protein that promotes inflammation and is produced in the liver as a result of interleukin-6 and IL-1b activation [17, 18]. Fibrinogen is converted to fibrin by activated thrombin in the coagulation cascade and can regulate the development of malignant tumors [19]. Recent research has confirmed that plasma fibrinogen levels play an oncogenic role in a variety of human cancers [20,21,22,23]. NLR (neutrophil–lymphocyte ratio) has become a prognostic indicator for many malignant tumors, and a high NLR often shortens the survival of patients [24,25,26]. Alternatively, NLR could be used as an independent prognostic indicator in patients with OSCC [27]. A recent meta-analysis of 17 studies with 4597 patients showed that pre-treatment NLR correlates with a statistically significant decrease of OS in head and neck squamous cell carcinoma patients [28]. The generation of inflammatory cytokines/chemokines by neutrophils facilitates the occurrence and development of tumors by creating a suitable tumor microenvironment [29]. Currently, there is no data on the combined parameters of plasma fibrinogen and NLR in the preoperative environment to predict the prognosis of OSCC.

The objective of this research was to determine the prognostic significance of F-NLR (combined fibrinogen and NLR score) in patients with OSCC. This work will generate fresh insight into the clinical efficacy of a composite score based on F-NLR as a prognostic factor of OSCC.

Methods

Materials and methods

A total of 365 individuals with OSCC treated with radical resection at the Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from February 2014 to November 2019 were enrolled in this retrospective analysis. The eligibility criteria included patients who had (1) a confirmed pathological diagnosis of OSCC; (2) no history of cancer; (3) no distant metastasis; (4) standard surgical approach: including primary tumor resection and neck dissection; (5) available clinical data and follow-up data; (6) no other conditions that could cause the blood values to change; and (7) no adjuvant radiotherapy or chemotherapy preoperatively. Patients with missing or partial data were excluded from the research. Preoperative medical and blood tests, as well as other necessary examinations, were performed on these patients to aid in the proper planning of surgery.

Blood assessment for determination of fibrinogen and NLR

One week before the start of treatment, blood samples were taken. The blood samples were immediately sent to the laboratory for testing of relevant indicators. Neutrophils and lymphocytes were measured using a SYSMEX Analyzer CS5100, Japan. Plasma fibrinogen concentrations were detected by a SYSMEX analyzer XN-9000, Japan. The measured indices were recorded, and the NLR is indicated as the neutrophil count/lymphocyte count.

Calculation of prognostic scores

The cutoff threshold for fibrinogen based on our study was 250 mg/dL. The cutoff threshold of NLR based on our data was 3.2. The F-NLR score was classified into three groups: F-NLR of 2, with hyperfibrinogenemia (> 250 mg/dL) and high NLR (> 3.2); F-NLR of 1, with only one higher index; and F-NLR of 0, with neither hyperfibrinogenemia nor high NLR.

Follow-up

Follow-up was performed monthly for the first 6 months and then every 6 months via telephone follow-up or clinical follow-up. From the time of surgery to death because of OSCC, the duration of cancer-specific survival (CSS) was recorded.

Statistical analysis

Univariable and multivariable analyses were used to evaluate clinical factors for CSS. Categorical data were analyzed by the chi-square test or Fisher’s exact test. Continuous data were compared by the Mann–Whitney U test. Multivariate Cox regression analysis and Kaplan–Meier analysis were utilized to assess CSS of OSCC. All data analyses were performed with SPSS (IBM SPSS 22.0, SPSS Inc.). Statistical tests were two-sided and considered significant with a P value < 0.05.

Results

Demographic data

A total of 365 patients who were eligible to participate were included in this study. The age of treatment ranged from 21 to 90 years, with males averaging 64 years and females averaging 63 years. A total of 174 (47.7%) of the patients were females, whereas 191 (52.3%) were males. Tumor size ≤ 4 cm (80.0%) and no lymph node metastases (78.4%) were the most common clinicopathological characteristics (Table 1).

Table 1 Comparison of clinical characteristics of the enrolled subjects (n = 365)
Full size table

ROC analysis

We identified the survival prediction values of fibrinogen, NLR and F-NLR using ROC curve analysis. Figure 1 shows the ROC curves and AUC results: the curve of fibrinogen (AUC = 0.649, 95% CI 0.585–0.741, and cutoff value = 250 mg/dL); the curve of NLR (AUC = 0.625, 95% CI 0.548–0.702, and cutoff value = 3.2); and the curve of F-NLR (AUC = 0.713, and 95% CI 0.649–0.788). Preoperative F-NLR showed a relatively better predictive role in oral cancer prognosis than fibrinogen and NLR alone (Fig. 1).

Fig. 1
figure 1

ROC curve for fibrinogen, NLR and F-NLR in OSCC patients. Fibrinogen, NLR, and F-NLR were the test variables, and CSS was the state variable. The areas under the curve are 0.649, 0.625 and 0.713, respectively. ROC receiver operating characteristic, F-NLR combined fibrinogen and NLR score, NLR neutrophil-to-lymphocyte ratio, CSS cancer-specific survival, OSCC oral squamous cell carcinoma, F fibrinogen

Full size image

Correlation of fibrinogen and NLR with clinicopathological characteristics

Patients were divided into three groups according to F-NLR (0, n = 100; 1, n = 203; 2, n = 62). The clinicopathological characteristics of the patients in the three groups are listed in Table 2. Higher F-NLRs were associated with tumor size (P = 0.0301), cervical node metastasis (P = 0.0039) and lymphatic and vascular invasion (LVI) (P = 0.0009).

Table 2 The clinicopathological characteristics stratified by the F-NLR score
Full size table

Risk factors for the prognosis of OSCC

Fourteen clinicopathological parameters were included in the univariate analyses, and nine significant parameters for univariate analysis were included in the multivariate analyses (Table 3). Multivariate analysis showed that F-NLR was an independent prognostic factor for cancer-specific survival (HR for F-NLR 1 and F-NLR 2: 26.566 and 3.895; 95% CI 5.589–126.258 and 1.321–11.485; P < 0.001 and P = 0.014, respectively). Patients with high F-NLR had a poor prognosis (Fig. 2).

Table 3 Univariate and multivariate analyses of prognostic factors in 365 patients with OSCC
Full size table
Fig. 2
figure 2

Kaplan–Meier curves for CSS according to F-NLR (A), fibrinogen (B), and NLR (C) in OSCC patients. F-NLR combined fibrinogen and NLR score, NLR neutrophil-to-lymphocyte ratio, CSS cancer-specific survival, OSCC oral squamous cell carcinoma

Full size image

In a stratified analysis based on tumor size and lymph node metastasis, the results showed that the prognostic value of F-NLR was maintained for T1–T2 (P < 0.0001, Fig. 3A), N (−) (P = 0.0234, Fig. 3C) and N (+) (P < 0.0001, Fig. 3D) tumors, except for T3–T4 (P = 0.0620, Fig. 3B) tumors.

Fig. 3
figure 3

CSS based on F-NLR in OSCC patients with T1–T2 tumors (A), patients with T3–T4 tumors (B), patients with lymphatic metastasis (C) and patients without lymphatic metastasis (D). F-NLR combined fibrinogen and NLR score, NLR neutrophil-to-lymphocyte ratio, CSS cancer-specific survival, OSCC oral squamous cell carcinoma

Full size image

Discussion

Oral cancer is the world's 11th most prevalent cancer [30]. Diagnosis at the early stage is critical for improving patient survival rates. When identified early, the survival probability is approximately 80–90% [31]. Therefore, it is critical to assess patients' prognostic variables before surgery. Plasma biomarkers have great potential for predicting tumor recurrence, because they can help surgeons make more individualized treatment plans [32]. Furthermore, these markers can be collected through standard blood testing prior to surgery, which is both cost effective and convenient.

Patients with cancer frequently have a better prognosis when there is no inflammation. The detection of circulating cell components is the most common method for measuring the degree of activation of the systemic inflammatory response [33]. For several common peripheral blood-derived inflammation scores, neutrophils play an active role in promoting tumor progression [34]. TILs play important roles in the progression of OSCC. Three main immunophenotypes are currently recognized according to the distribution of T cells in the tumor: immune-inflamed, immune-excluded, and immune-desert [35]. Immune-inflamed tumors are characterized by a dense infiltration of immune cells in close proximity to tumor cells. Immune-excluded tumors are characterized by the presence of large numbers of immune cells that do not penetrate the tumor parenchyma but remain in the stroma. The immune-desert phenotype is characterized by an almost complete absence of immune cells in the tumor parenchyma or stroma. Troiano et al. demonstrated that squamous cell carcinoma of the tongue patients with an immune-desert phenotype had lower survival [36]. Based on the above results, lymphocytes can significantly inhibit the proliferation of tumors [37]. Therefore, the NLR can serve as a reliable tumor prognostic factor. Numerous studies have confirmed that NLR is a prognostic factor for a variety of benign and malignant tumors and a representative indicator of tumor-associated inflammation, and NLR has been shown to have predictive value for oral cancer [38,39,40,41]. Activation of the coagulation cascade has a substantial effect on the development of cancer, and fibrinogen has been shown to be one of the regulators of systemic inflammation and tumor progression [42, 43]. These studies have laid a solid foundation for the next step to explore the role of inflammatory factors in the prognosis of oral cancer. In this study, patients with advanced tumors tended to have a high fibrinogen level and high NLR. In addition, high fibrinogen and high NLR were found to be important indicators for predicting clinical outcome in this study (P < 0.001 and P = 0.008). The results of our study are consistent with those of previous meta-analyses, showing that high NLR significantly reduces the survival time of head and neck squamous cell carcinoma patients [28]. We propose the following mechanism of action: Fibrinogen may function by forming a protective framework that facilitates tumor migration, invasion, and angiogenesis. Tumor cells create an inflammatory state in the body and accelerate the production of fibrinogen in the liver, thus forming a vicious cycle.

We also confirmed that age, tumor size, and cervical nodal metastasis are independent prognostic factors for oral squamous cell carcinoma, as previously reported by Broglie et al. [44] and Patel et al. [45]. Interestingly, the multivariate analysis showed that different MPV (mean platelet volume) levels can also significantly affect the prognosis of oral cancer. MPV is an indicator of platelet activation and has been found to be a prognostic indicator in a variety of cancers [46]. The value of MPV as a prognostic indicator may be that activated platelets promote the secretion of cytokines, such as platelet-derived endothelial cell growth factor, which accelerates tumorigenesis [47]. In a study observed over 30 years, Zanoni et al. found that perineural invasion (PNI) and lymphatic and vascular invasion (LVI) were independent prognostic factors of OSCC [48]. However, unlike the previous study, our data analysis showed that only LVI was prognostic factor for OSCC, but PNI was not statistically different. The reason may be that we only have nine PNI positive patients, and analyses with larger sample sizes require further validation.

The new scoring system (F-NLR) is a good predictor for the prognosis of a variety of malignancies. Wang et al. proved that F-NLR can independently predict the prognosis of patients with non-small-cell lung cancer [49]. Data from Felice's studies showed that F-NLR is substantially related to worse survival results in individuals with anal canal cancer [50]. The above research has established that the F-NLR is a reliable scoring system for assessing malignant tumors. No detailed investigation of the application prospects of the F-NLR scoring system in oral cancer has been performed. Therefore, this retrospective study was performed to identify the association of F-NLR with prognosis after radical resection of oral cancer.

For predictive analysis following radical excision of oral cancer, we separated the patients with different F-NLR into three independent groups. The results suggested that F-NLR, as predicted, can identify more individuals with a worse prognosis than fibrinogen or NLR alone. This finding demonstrates that F-NLR may be more reliable than individual scores. The median survival times were 62 months (scores of 0) and 41 months (scores of 1–2), respectively. Patients with high F-NLR had a substantially poorer prognosis than those with low scores. Meanwhile, these data show that F-NLR is connected to tumor development and aggressiveness. In our subgroup analyses, F-NLR was a good prognostic factor; for example, in patients with T1–T2 tumor sizes and different lymph node metastases, the F-NLR scoring system showed a good prognostic effect.

This study has some limitations. First, a single-center retrospective study may lead to selection bias. Second, the short follow-up period was not sufficient to further assess the survival of patients. Consequently, a more comprehensive multicenter prospective study is needed to confirm that F-NLR does independently predict prognosis in patients with OSCC.

According to the findings of this study, F-NLR has clinical promise as a low-cost prognostic factor in patients with OSCC.

Conclusion

This study suggests that the F-NLR is an independent prognostic indicator for the survival rate of OSCC.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

Abbreviations

OSCC:

Oral squamous cell carcinoma

F-NLR:

Combined fibrinogen and NLR score

NLR:

Neutrophil-to-lymphocyte ratio

AUC:

Area under the receiver operating characteristic curve

CI:

Confidence interval

ROC:

Receiver operating characteristic

CSS:

Cancer-specific survival

TILs:

Tumor-infiltrating lymphocytes

MPV:

Mean platelet volume

PNI:

Perineural invasion

LVI:

Lymphatic and vascular invasion

References

  1. Harada H, Tomioka H, Hirai H, Kuroshima T, Oikawa Y, Nojima H, Sakamoto J, Kurabayashi T, Kayamori K, Ikeda T. MRI before biopsy correlates with depth of invasion corrected for shrinkage rate of the histopathological specimen in tongue carcinoma. Sci Rep. 2021;11(1):20992–20992.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Li G, Wang X, Li C, Hu S, Niu Z, Sun Q, Sun M. Piwi-interacting RNA1037 enhances chemoresistance and motility in human oral squamous cell carcinoma cells. Onco Targets Ther. 2019;12:10615–27.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Annertz K, Anderson H, Palmér K, Wennerberg J. The increase in incidence of cancer of the tongue in the Nordic countries continues into the twenty-first century. Acta Otolaryngol. 2012;132(5):552–7.

    Article  PubMed  Google Scholar 

  4. Bekes EM, Schweighofer B, Kupriyanova TA, Zajac E, Ardi VC, Quigley JP, Deryugina EI. Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation. Am J Pathol. 2011;179(3):1455–70.

    Article  PubMed  PubMed Central  Google Scholar 

  5. McDonald B, Spicer J, Giannais B, Fallavollita L, Brodt P, Ferri LE. Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. Int J Cancer. 2009;125(6):1298–305.

    Article  PubMed  Google Scholar 

  6. Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P, Ferri LE. Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Can Res. 2012;72(16):3919–27.

    Article  Google Scholar 

  7. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  PubMed  Google Scholar 

  8. Boxberg M, Leising L, Steiger K, Jesinghaus M, Alkhamas A, Mielke M, Pfarr N, Götz C, Wolff KD, Weichert W, et al. Composition and clinical impact of the immunologic tumor microenvironment in oral squamous cell carcinoma. J Immunol. 2019;202(1):278–91.

    Article  PubMed  Google Scholar 

  9. Quan H, Shan Z, Liu Z, Liu S, Yang L, Fang X, Li K, Wang B, Deng Z, Hu Y, et al. The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction. Cancer Immunol Immunother CII. 2020;69(3):465–76.

    Article  PubMed  Google Scholar 

  10. Zhou C, Wu Y, Jiang L, Li Z, Diao P, Wang D, Zhang W, Liu L, Wang Y, Jiang H, et al. Density and location of CD3(+) and CD8(+) tumor-infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2018;47(4):359–67.

    Google Scholar 

  11. Fang J, Li X, Ma D, Liu X, Chen Y, Wang Y, Lui VWY, Xia J, Cheng B, Wang Z. Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma. BMC Cancer. 2017;17(1):375.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4:59.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hall M, Liu H, Malafa M, Centeno B, Hodul PJ, Pimiento J, Pilon-Thomas S, Sarnaik AA. Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. J Immunother Cancer. 2016;4:61.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cohen JT, Miner TJ, Vezeridis MP. Is the neutrophil-to-lymphocyte ratio a useful prognostic indicator in melanoma patients? Melanoma Manag. 2020;7(3):MMT47.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Corbeau I, Jacot W, Guiu S. Neutrophil to lymphocyte ratio as prognostic and predictive factor in breast cancer patients: a systematic review. Cancers. 2020;12(4):958.

    Article  PubMed Central  Google Scholar 

  16. Stefaniuk P, Szymczyk A, Podhorecka M. The neutrophil to lymphocyte and lymphocyte to monocyte ratios as new prognostic factors in hematological malignancies - a narrative review. Cancer Manag Res. 2020;12:2961–77.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Vilar R, Fish RJ, Casini A, Neerman-Arbez M. Fibrin(ogen) in human disease: both friend and foe. Haematologica. 2020;105(2):284–96.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yamaguchi T, Kimura H, Yokota S, Yamamoto Y, Hashimoto T, Nakagawa M, Ito M, Ogura T. Effect of IL-6 elevation in malignant pleural effusion on hyperfibrinogenemia in lung cancer patients. Jpn J Clin Oncol. 2000;30(2):53–8.

    Article  PubMed  Google Scholar 

  19. Weisel JW, Litvinov RI. Fibrin formation, structure and properties. Subcell Biochem. 2017;82:405–56.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang M, Zhang G, Zhang Y, Cui X, Wang S, Gao S, Wang Y, Liu Y, Bae JH, Yang W-H, et al. Fibrinogen alpha chain knockout promotes tumor growth and metastasis through integrin-AKT signaling pathway in lung cancer. Mol Cancer Res MCR. 2020;18(7):943–54.

    Article  PubMed  Google Scholar 

  21. Palumbo JS, Degen JL. Fibrinogen and tumor cell metastasis. Haemostasis. 2001;31(Suppl 1):11–5.

    PubMed  Google Scholar 

  22. Chan JP, Merlini M, Gao H-X, Mendiola AS, Akassoglou K, Rubenstein JL, Ryu JK. Blood coagulation factor fibrinogen in tumor pathogenesis of central nervous system B-cell lymphoma. Am J Pathol. 2021;191(3):575–83.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Palumbo JS, Talmage KE, Liu H, La Jeunesse CM, Witte DP, Degen JL. Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patency. Blood. 2003;102(8):2819–27.

    Article  PubMed  Google Scholar 

  24. Diem S, Schmid S, Krapf M, Flatz L, Born D, Jochum W, Templeton AJ, Früh M. Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer. 2017;111:176–81.

    Article  PubMed  Google Scholar 

  25. Franz L, Alessandrini L, Fasanaro E, Gaudioso P, Carli A, Nicolai P, Marioni G. Prognostic impact of neutrophils-to-lymphocytes ratio (NLR), PD-L1 expression, and tumor immune microenvironment in laryngeal cancer. Ann Diagn Pathol. 2021;50: 151657.

    Article  PubMed  Google Scholar 

  26. Schwartz PB, Poultsides G, Roggin K, Howard JH, Fields RC, Clarke CN, Votanopoulos K, Cardona K, Winslow ER. PLR and NLR are poor predictors of survival outcomes in sarcomas: a new perspective from the USSC. J Surg Res. 2020;251:228–38.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tazeen S, Prasad K, Harish K, Sagar P, Kapali AS, Chandramouli S. Assessment of pretreatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in prognosis of oral squamous cell carcinoma. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2020;78(6):949–60.

    Article  Google Scholar 

  28. Mariani P, Russo D, Maisto M, Troiano G, Caponio VCA, Annunziata M, Laino L. Pre-treatment neutrophil-to-lymphocyte ratio is an independent prognostic factor in head and neck squamous cell carcinoma: Meta-analysis and trial sequential analysis. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2022;51(1):39–51.

    Google Scholar 

  29. Gregory AD, Houghton AM. Tumor-associated neutrophils: new targets for cancer therapy. Can Res. 2011;71(7):2411–6.

    Article  Google Scholar 

  30. D’Souza S, Addepalli V. Preventive measures in oral cancer: an overview. Biomed Pharmacother Biomed Pharmacother. 2018;107:72–80.

    Article  PubMed  Google Scholar 

  31. Bagan J, Sarrion G, Jimenez Y. Oral cancer: clinical features. Oral Oncol. 2010;46(6):414–7.

    Article  PubMed  Google Scholar 

  32. Huang Z, Ma L, Huang C, Li Q, Nice EC. Proteomic profiling of human plasma for cancer biomarker discovery. Proteomics. 2017;17(6):1600240.

    Article  Google Scholar 

  33. Yamamoto M, Kurokawa Y, Kobayashi N, Takahashi T, Miyazaki Y, Tanaka K, Makino T, Yamasaki M, Nakajima K, Mori M, et al. Prognostic value of the combined index of plasma fibrinogen and the neutrophil-lymphocyte ratio in gastric cancer. World J Surg. 2020;44(1):207–12.

    Article  PubMed  Google Scholar 

  34. Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120(4):1151–64.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res Off J Am Assoc Cancer Res. 2016;22(8):1865–74.

    Article  Google Scholar 

  36. Troiano G, Rubini C, Togni L, Caponio VCA, Zhurakivska K, Santarelli A, Cirillo N, Lo Muzio L, Mascitti M. The immune phenotype of tongue squamous cell carcinoma predicts early relapse and poor prognosis. Cancer Med. 2020;9(22):8333–44.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410(6832):1107–11.

    Article  PubMed  Google Scholar 

  38. Hirahara T, Arigami T, Yanagita S, Matsushita D, Uchikado Y, Kita Y, Mori S, Sasaki K, Omoto I, Kurahara H, et al. Combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with advanced gastric cancer. BMC Cancer. 2019;19(1):672.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wan J, Wang X, Zhen Y, Chen X, Yao P, Liu W, Lu E, Du Y, Liu H, Zhao S. The predictive role of the neutrophil-lymphocyte ratio in the prognosis of adult patients with stroke. Chin Neurosurg J. 2020;6:22.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zhang N, Jiang J, Tang S, Sun G. Predictive value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Int Immunopharmacol. 2020;85: 106677.

    Article  PubMed  Google Scholar 

  41. Abbate V, Dell’Aversana Orabona G, Salzano G, Bonavolontà P, Maglitto F, Romano A, Tarabbia F, Turri-Zanoni M, Attanasi F, Di Lauro AE, et al. Pre-treatment Neutrophil-to-Lymphocyte Ratio as a predictor for occult cervical metastasis in early stage (T1–T2 cN0) squamous cell carcinoma of the oral tongue. Surg Oncol. 2018;27(3):503–7.

    Article  PubMed  Google Scholar 

  42. Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev. 2015;29(1):17–24.

    Article  PubMed  Google Scholar 

  43. Repetto O, De Re V. Coagulation and fibrinolysis in gastric cancer. Ann N Y Acad Sci. 2017;1404(1):27–48.

    Article  PubMed  Google Scholar 

  44. Ng JH, Iyer NG, Tan MH, Edgren G. Changing epidemiology of oral squamous cell carcinoma of the tongue: a global study. Head Neck. 2017;39(2):297–304.

    Article  PubMed  Google Scholar 

  45. Patel KB, Martin D, Zhao S, Kumar B, Carrau R, Ozer E, Agrawal A, Kang S, Rocco JW, Schuller D, et al. Impact of age and comorbidity on survival among patients with oral cavity squamous cell carcinoma. Head Neck. 2021;43(1):268–77.

    Article  PubMed  Google Scholar 

  46. Pyo JS, Sohn JH, Kang G. Diagnostic and prognostic roles of the mean platelet volume in malignant tumors: a systematic review and meta-analysis. Platelets. 2016;27(8):722–8.

    Article  PubMed  Google Scholar 

  47. Yagyu T, Saito H, Sakamoto T, Uchinaka E, Morimoto M, Hanaki T, Watanabe J, Matsunaga T, Yamamoto M, Tokuyasu N, et al. Decreased mean platelet volume predicts poor prognosis in patients with pancreatic cancer. BMC Surg. 2021;21(1):8.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Zanoni DK, Montero PH, Migliacci JC, Shah JP, Wong RJ, Ganly I, Patel SG. Survival outcomes after treatment of cancer of the oral cavity (1985–2015). Oral Oncol. 2019;90:115–21.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wang H, Zhao J, Zhang M, Han L, Wang M, Xingde L. The combination of plasma fibrinogen and neutrophil lymphocyte ratio (F-NLR) is a predictive factor in patients with resectable non small cell lung cancer. J Cell Physiol. 2018;233(5):4216–24.

    Article  PubMed  Google Scholar 

  50. De Felice F, Rubini FL, Romano L, Bulzonetti N, Caiazzo R, Musio D, Tombolini V. Prognostic significance of inflammatory-related parameters in patients with anal canal cancer. Int J Colorectal Dis. 2019;34(3):519–25.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was supported by grants from the Science and Technology Development Fund of Nanjing Medical University (Grant No. NMUB2020140).

Author information

Author notes

  1. Meng Wu, Pu Ye and Wei Zhang equally contributed to this article and should be regarded as co-first authors

Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, No. 1, Huanghe West Road, Huaian, 223300, Jiangsu Province, China

    Meng Wu, Pu Ye, Wei Zhang & Huiming Yu

  2. Department of Pharmacy, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, 223300, Jiangsu Province, China

    Hong Zhu

Authors
  1. Meng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pu Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huiming Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HY conceived the study, carried out the study design and coordination, wrote the manuscript, and gave the final approval of the version of the manuscript to be submitted. MW and HZ critically revised the manuscript for important intellectual content. WZ and PY collected the clinical data and drafted the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Huiming Yu.

Ethics declarations

Ethics approval and consent to participate

All participants gave written informed consent. This study was conducted according to the Declaration of Helsinki and was approved by the Institutional Ethics Committee of the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University.

Consent to publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, M., Ye, P., Zhang, W. et al. Prognostic role of an inflammation scoring system in radical resection of oral squamous cell carcinoma. BMC Oral Health 22, 226 (2022). https://doi.org/10.1186/s12903-022-02261-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12903-022-02261-8

Keywords

BMC Oral Health

ISSN: 1472-6831

Contact us