Elevated neutrophil to lymphocyte and platelet to lymphocyte ratios predict high grade and advanced stage renal cell carcinoma
Selahattin Çalışkan First Published March 11, 2019 Research Article
https://doi.org/10.1177/1724600818817557
Article information
Open Access Creative Commons Attribution, Non Commercial 4.0 License
Abstract
Introduction:
Renal cell carcinoma is the most common malignancy of the kidney, which accounts 85% of all renal tumors. In recent years, the incidence of renal cell carcinoma was increased due to the widespread use of imaging techniques. The aim of this study is to investigate the clinical significance of pretreatment neutrophil to lymphocyte and platelet to lymphocyte ratios in patients with renal cell carcinomas.
Methods:
The patients who underwent nephrectomy for renal tumor between 2010 and 2018 in two centers were reviewed retrospectively. The age, sex, complete blood test, and pathological results were recorded. The patients who were diagnosed with other carcinomas, benign renal tumors, and missing data of age, complete blood test, and pathological results, were excluded. The patients were divided into two groups according to the T stage and Fuhrman grade, T1-2 and T3-4, G1-2 and G3-4.
Results:
There were 271 patients in the current study. The male to female ratio was 1.97 and the mean age of the patients was 59.37±11.62 years. Clear cell renal cell carcinoma was the most common subtype in 72.7% of the patients. Both the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio were significantly higher in patients with high-grade and advanced-stage disease than in the others. The receiver operating characteristic curve showed no significant difference between platelet to lymphocyte ratio and neutrophil to lymphocyte ratio to diagnose the high grade and stage of renal cell carcinoma.
Conclusion:
The neutrophil to lymphocyte and platelet to lymphocyte ratios are easily accessible biomarkers which are used for the prognosis of malignancy. The current study found that these biomarkers may predict the pathological results during the preoperative period.
Keywords Neutrophil to lymphocyte ratio, renal cell carcinoma, platelet to lymphocyte ratio
Introduction
Kidney and renal pelvis cancers account for 3% of all adult tumors.1 Renal cell carcinoma (RCC) is the seventh and ninth most common cancer in male and female patients, respectively.2 RCC is predominantly seen in males and is diagnosed between 50 and 70 years of age.3 Studies have shown that inflammation plays an important role in the pathogenesis and progression of RCC,2 and that neutrophils and platelets have a prominent role in the inflammation of tumors and immunology.4 Neutrophils can induce tumor growth and remodel the extracellular matrix for metastasis. In addition, reactive oxygen species, nitric oxide, and arginase are released by neutrophils. Tumor cells produce hematopoietic cytokines that increase the neutrophil levels. Platelets release a vascular endothelial growth factor, which is important in angiogenesis for tumor growth. Platelets may also protect cancer cells from the immune system and secrete thrombospondin to facilitate tumor adhesion and extravasation.5
The platelet to lymphocyte ratio (PLR) and the neutrophil to lymphocyte ratio (NLR) are useful biomarkers to predict survival in patients with malignant neoplasm.1 These biomarkers have been found to be associated with the oncologic outcomes in some malignancies including colorectal, ovarian, testicular, and renal cell cancers.6–9 In this study, I investigated the relationship between PLR, NLR, and the pathological results of the patients with RCC.
Materials and methods
The patients who underwent radical or partial nephrectomy for renal tumor between 2010 and 2018 in two centers; Haydarpaşa Numune Training and Research Hospital and Hitit University, Çorum Erol Olçok Training and Research Hospital, were reviewed retrospectively. The age, sex, complete blood test before surgery, and the pathological results were recorded. The PLR and the NLR were calculated by dividing the platelet count by the lymphocyte, and the neutrophil count by the lymphocyte count, respectively. Normal hematological reference values for neutrophils, platelets, and lymphocytes were 2–7, 100–300 and 1–4 *109/l, respectively. Venous blood samples were taken by antecubital venipuncture containing ethylenediaminetetraacetic acid as an anticoagulant. A full blood count was measured as standard laboratory procedure using an LH780 automated cell counter (Beckman Coulter, Pasadena, CA, USA).
The patients who had a diagnosis of (a) benign renal tumor; (b) other kidney cancers such as squamous and transitional; (c) hematologic disease; (d) received anticoagulant drugs; and (e) active infection, were excluded from the study.
The surgical specimens were evaluated by genitourinary pathologists. The Fuhrman grade system, TNM classification (7th edition from American Joint Committee, 2017) and histologic subtype (World Health Organization, 2016) were used for pathological result. The patients were divided into two groups according to the low and high T-stage and Fuhrman grade, as T1-T2 and T3-T4, G1-2 and G3-4, respectively. The platelet to lymphocyte ratio and neutrophil to lymphocyte ratio were compared between T1-T2 and T3-T4, G1-G2 and G3-G4. The receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic efficacy of PLR, NLR, platelet, neutrophil, and lymphocyte for advanced stage and high grade.
Distribution normality was analyzed with the Kolmogorov-Smirnov test. The normal distribution variable was compared with independent t test and the others were compared with Mann-Whitney U test. The chi-squared test was used for percentage values. Data were expressed as mean ± standard deviation for age, median for the others, and P < 0.05 as considered with statistical significance. Statistical analyses were performed using the demo version of MedCalc Statistical Software version 17.6 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2017).
Results
There were 271 patients in the study. Of these patients, 180 were male and 91 were female. The mean age of the patients was 59.37±11.62 years. Table 1 shows the characteristics and pathological results of the patients. The advanced stage (T3-T4) was reported in 64 patients (23.61%), and the Fuhrman grading system was reported in 258 patients: 48.83% had high grade (G3-G4). Table 2 shows the hematological parameters according to the grade and T stage classification. Both PLR and NLR were higher in patients with a more advanced stage and a higher grade than the others. The platelet was significantly higher in patients with T3-T4. The tumor size was correlated with T stage and Fuhrman grade.
Table
Table 1. The characteristics of the patients.
Table 1. The characteristics of the patients.
View larger version
Table
Table 2. The hematological parameters and patients’ characteristics according to the grade and T stage classification.
Table 2. The hematological parameters and patients’ characteristics according to the grade and T stage classification.
View larger version
The ROC analysis is shown in Figure 1. There was no significant difference between NLR and PLR to predict the stage and grade (P=0.07). The area under curve (AUC) was greater for PLR to predict the advanced stage than for the others. There was a significant difference between PLR and lymphocyte (P=0.001). The lymphocyte had the biggest AUC for advanced stage diagnosis (0.605), and a significant difference was detected between PLR and platelet (P=0.01). The AUC of the hematological parameters are seen in Table 3.
figure
Figure 1. The ROC of the parameters. ROC: receiver operating characteristic.
Table
Table 3. The AUC of the hematological parameters in advanced stage and high grade.
Table 3. The AUC of the hematological parameters in advanced stage and high grade.
View larger version
Discussion
The incidence of RCC has increased in the last three decades.10 The widespread use of radiologic imaging techniques may be one of the reasons for this increase.11 The other factors are environmental exposures, smoking, obesity, and changes in lifestyle. Surgery is the gold standard treatment for patients with localized disease, but 10%–60% of the patients develop recurrence after surgery.10 Although several prognostic factors have been reported for RCC, the stage and grade are the most important factors.11
In the pathophysiology of the cancer-associated systemic inflammation, the distribution of circulating inflammatory cells changes.12 The main change is neutrophilia with relative lymphocytopenia or thrombocytosis. Neutrophils secrete some cytokines including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, and vascular endothelial growth factor (VEGF), which is a proangiogenic factor.10 They also release reactive oxygen species, nitric oxide, and arginase.4 The neutrophils promote tumor growth and metastasis by remodeling the extracellular matrix and suppressing the T-cell response. Additionally, tumor cells produce immunosuppressive cytokines, which decrease the cytotoxic T lymphocytes.13 As a result, the decreased lymphocyte count causes suboptimal defense in the lymphocyte-mediated immune system against cancer. The platelets have a prominent role in cancer progression. They promote tumor growth and angiogenesis by VEGF cytokine.4 VEGF induces the formation of blood vessels and facilitates metastasis.14 Solid tumors produce IL-6, which contributes to the thrombocytosis. The IL-6 stimulates thrombopoietin that increases the platelet count in patients with malignancy.15 The other cytokines are IL-11, stem cell factor, and granulocyte-macrophage colony-stimulating factor.16
Some prognostic factors, such as NLR and PLR, which came from the blood cells, have been defined as valuable biomarkers to predict the prognosis in solid tumors.17 These biomarkers are cheap and easily acquired when compared with other markers such as C-reactive protein.18 The authors investigated the NLR in patients with metastatic RCC and found NLR>4 was independently associated with overall survival.19 The other study showed that high NLR (⩾1.7) was correlated both worse overall and disease-free survival in non-metastatic RCC.20 In addition, the authors found that preoperative NLR was associated with increased risk of death and all-cause mortality in patients with localized clear cell RCC.10 Most of the studies about NLR and RCC are about the prognosis, the clinical diagnosis and importance is limited in the literature. Otunctemur et al.3 reported that NLR was higher in patients with advanced stage and high grade (T3-4, G3-4) than the others. The authors found similar results; NLR value was significantly higher in patients with advanced disease and high grade of RCC.21 The current study showed that NLR was significantly higher in patients with advanced stage and high-grade disease (P<0.05).
In a meta-analysis; the authors reported that elevated PLR was associated with poor overall survival and disease-free survival in renal cancer.18 The other meta-analysis indicated that elevated PLR is an independent predictor of poor overall survival and progression-free survival in RCC.17 Baum et al. found that elevated PLR was associated with short survival.22 Dirikan et al., from Turkey, revealed that patients diagnosed with metastatic RCC with high PLR had shorter overall survival than the others without significant difference.23 In another study from the UK, the investigators found that high PLR was associated with high grade (G3), high T stage (T2+), and large tumor size (⩾3 cm).12 The authors reported that elevated PLR was associated with high grade (G3-4) and advanced T stage (T3-4) of RCC.21 In addition, PLR was found to be significantly increased in the advanced stage (III-IV) of ovarian cancer.5 The current study showed that elevated PLR was associated with high grade and advanced stage disease (P<0.05).
There are some limitations in the current study. The retrospective design, which is associated with selection bias and incomplete data collection, is the main limitation. Also, overall survival and cancer-specific survival was not evaluated. These limitations include a relatively large series of RCCs from Turkey regarding the clinical significance of PLR and NLR for the pathology of RCC.
In conclusion, the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio may predict the pathological outcome for patients with RCCs. Further studies are needed to understand the role of these ratios in the pathology of RCCs.
Authors’ Note
Selahattin Çalışkan is now affiliated with Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey.
Declaration of conflicting interest
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
References
1. Fukuda, H, Takagi, T, Kondo, T. Predictive value of inflammation based prognostic scores in patients with metastatic renal cell carcinoma treated with cytoreductive nephrectomy. Oncotarget 2018; 9: 14296–14305.
Google Scholar | Medline
2. Wang, X, Su, S, Guo, Y. The clinical use of the platelet to lymphocyte ratio and lymphocyte to monocyte ratio as prognostic factors in renal cell carcinoma: a systematic review and meta-analysis. Oncotarget 2017; 8: 84506–84514.
Google Scholar | Medline
3. Otunctemur, A, Dursun, M, Besiroğlu, H. Clinical significance of preoperative neutrophil to lymphocyte ratio in renal cell carcinoma. Int Braz J Urol 2016; 42: 678–684.
Google Scholar | Medline
4. Kemal, Y, Yucel, I, Ekiz, K. Elevated serum neutrophil to lymphocyte and platelet to lymphocyte ratios could be useful in lung cancer diagnosis. Asian Pac J Cancer Prev 2014; 15: 2651–2654.
Google Scholar | Medline
5. Kokcu, A, Kurtoglu, E, Celik, H. May the platelet to lymphocyte ratio be a prognostic factor for epithelial ovarian cancer? Asian Pac J Cancer Prev 2014; 15: 9781–9784.
Google Scholar | Medline
6. Walsh, SR, Cook, EJ, Goulder, F. Neutrophil lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 2005; 91: 181–184.
Google Scholar | Medline | ISI
7. Thavarama, T, Phaloprakarn, C, Tangjitgamol, S. Role of neutrophil to lymphocyte ratio as a prognostic indicator for epithelial ovarian cancer. J Med Assoc Thai 2011; 94: 871–877.
Google Scholar | Medline
8. Jankovich, M, Jankovichova, T, Ondrus, D. Neutrophil to lymphocyte ratio as a predictor of preoperative tumor staging in testicular germ cell tumors. Bratisl Med J 2017; 118: 510–512.
Google Scholar
9. Wojtas, AS, Lubas, A, Stec, R. Neutropil to lymphocyte ratio, platelet to lymphocyte ratio, C-reactive protein as new simple prognostic factors in patients with metastatic renal cell cancer treated with tyrosine kinase inhibitors: a systematic review and meta-analysis. Clin Genitourin Canc 2018; 16: 685–693.
Google Scholar
10. Viers, BR, Thompson, RH, Boorjan, SA. Preoperative neutrophil-lymphocyte ratio predicts death among patients with localized clear cell renal carcinoma undergoing nephrectomy. Urol Oncol-Semin Ori 2014; 32: 1277–1284.
Google Scholar | Medline
11. Seda, CJO, Salas, ASJ, Sanchez, CG. Thrombocytosis and hematocrit as prognostic factors in renal carcinoma. Arch Esp Urol 2011; 64: 883–890.
Google Scholar | Medline
12. Lee, SM, Russell, A, Hellawell, G. Predictive value of pretreatment inflammation based prognostic scores (neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and lymphocyte to monocyte ratio) for invasive bladder carcinoma. Korean J Urol 2015; 56: 745–799.
Google Scholar
13. Hu, K, Lou, L, Ye, J. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open 2015; 5: e006404.
Google Scholar | Medline | ISI
14. Kilincalp, S, Çoban, Ş, Akınc, H. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma. Eur J Cancer Prev 2015; 24: 328–333.
Google Scholar | Medline
15. Templeton, AJ, Ace, O, McNamara, MG. Prognostic role of platelet to lymphocyte ratio in solid tumors. A systematic review and meta-analysis. Canc Epidemiol Biomarkers Prev 2014; 23: 1204–1212.
Google Scholar | Medline | ISI
16. Choi, JY, Ko, YH, Song, PH. Clinical significance of preoperative thrombocytosis in patients who underwent radical nephrectomy for nonmetastatic renal cell carcinoma. Investig Clin Urol 2016; 57: 324–329.
Google Scholar | Medline
17. Wang, Z, Peng, S, Wang, A. Platelet lymphocyte ratio acts as an independent predictor of prognosis in patients with renal cell carcinoma. Clin Chim Acta 2018; 480: 166–172.
Google Scholar | Medline
18. Luo, Y, She, D, Xiong, H. Pretreatment neutrophil to lymphocyte ratio as a prognostic predictor of urologic tumors. Medicine (Baltimore) 2015; 94: e1670.
Google Scholar | Medline
19. Baum, YS, Patil, D, Huang, JH. Elevated preoperative neutrophil to lymphocyte ratio may be associated with decreased overall survival in patients with metastatic clear cell renal cell carcinoma undergoing cytoreductive nephrectomy. Asian J Urol 2015; 3: 20–25.
Google Scholar | Medline
20. Wen, RM, Zhang, YJ, Ma, S. Preoperative neutrophil to lymphocyte ratio as prognostic factor in patients with non-metastatic renal cell carcinoma. Asian Pac J Cancer Prev 2015; 16: 3703–3708.
Google Scholar | Medline
21. Peng, D, He, Z-s, Li, X-s. Prognostic value of inflammatory and nutritional scores in renal cell carcinoma after nephrectomy. Clin Genitourin Canc 2017; 15: 582–590.
Google Scholar | Medline
22. Wang, J, Liu, Y, Zhang, N. Prognostic role of pretreatment platelet to lymphocyte ratio in urologic cancer. Oncotarget 2017; 8: 70874–70882.
Google Scholar | Medline
23. Dirican, A, Kucukzeybek, Y, Somali, I. The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma. JBUON 2013; 18: 413–419.
Google Scholar
View Abstract
Selahattin Çalışkan First Published March 11, 2019 Research Article
https://doi.org/10.1177/1724600818817557
Article information
Open Access Creative Commons Attribution, Non Commercial 4.0 License
Abstract
Introduction:
Renal cell carcinoma is the most common malignancy of the kidney, which accounts 85% of all renal tumors. In recent years, the incidence of renal cell carcinoma was increased due to the widespread use of imaging techniques. The aim of this study is to investigate the clinical significance of pretreatment neutrophil to lymphocyte and platelet to lymphocyte ratios in patients with renal cell carcinomas.
Methods:
The patients who underwent nephrectomy for renal tumor between 2010 and 2018 in two centers were reviewed retrospectively. The age, sex, complete blood test, and pathological results were recorded. The patients who were diagnosed with other carcinomas, benign renal tumors, and missing data of age, complete blood test, and pathological results, were excluded. The patients were divided into two groups according to the T stage and Fuhrman grade, T1-2 and T3-4, G1-2 and G3-4.
Results:
There were 271 patients in the current study. The male to female ratio was 1.97 and the mean age of the patients was 59.37±11.62 years. Clear cell renal cell carcinoma was the most common subtype in 72.7% of the patients. Both the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio were significantly higher in patients with high-grade and advanced-stage disease than in the others. The receiver operating characteristic curve showed no significant difference between platelet to lymphocyte ratio and neutrophil to lymphocyte ratio to diagnose the high grade and stage of renal cell carcinoma.
Conclusion:
The neutrophil to lymphocyte and platelet to lymphocyte ratios are easily accessible biomarkers which are used for the prognosis of malignancy. The current study found that these biomarkers may predict the pathological results during the preoperative period.
Keywords Neutrophil to lymphocyte ratio, renal cell carcinoma, platelet to lymphocyte ratio
Introduction
Kidney and renal pelvis cancers account for 3% of all adult tumors.1 Renal cell carcinoma (RCC) is the seventh and ninth most common cancer in male and female patients, respectively.2 RCC is predominantly seen in males and is diagnosed between 50 and 70 years of age.3 Studies have shown that inflammation plays an important role in the pathogenesis and progression of RCC,2 and that neutrophils and platelets have a prominent role in the inflammation of tumors and immunology.4 Neutrophils can induce tumor growth and remodel the extracellular matrix for metastasis. In addition, reactive oxygen species, nitric oxide, and arginase are released by neutrophils. Tumor cells produce hematopoietic cytokines that increase the neutrophil levels. Platelets release a vascular endothelial growth factor, which is important in angiogenesis for tumor growth. Platelets may also protect cancer cells from the immune system and secrete thrombospondin to facilitate tumor adhesion and extravasation.5
The platelet to lymphocyte ratio (PLR) and the neutrophil to lymphocyte ratio (NLR) are useful biomarkers to predict survival in patients with malignant neoplasm.1 These biomarkers have been found to be associated with the oncologic outcomes in some malignancies including colorectal, ovarian, testicular, and renal cell cancers.6–9 In this study, I investigated the relationship between PLR, NLR, and the pathological results of the patients with RCC.
Materials and methods
The patients who underwent radical or partial nephrectomy for renal tumor between 2010 and 2018 in two centers; Haydarpaşa Numune Training and Research Hospital and Hitit University, Çorum Erol Olçok Training and Research Hospital, were reviewed retrospectively. The age, sex, complete blood test before surgery, and the pathological results were recorded. The PLR and the NLR were calculated by dividing the platelet count by the lymphocyte, and the neutrophil count by the lymphocyte count, respectively. Normal hematological reference values for neutrophils, platelets, and lymphocytes were 2–7, 100–300 and 1–4 *109/l, respectively. Venous blood samples were taken by antecubital venipuncture containing ethylenediaminetetraacetic acid as an anticoagulant. A full blood count was measured as standard laboratory procedure using an LH780 automated cell counter (Beckman Coulter, Pasadena, CA, USA).
The patients who had a diagnosis of (a) benign renal tumor; (b) other kidney cancers such as squamous and transitional; (c) hematologic disease; (d) received anticoagulant drugs; and (e) active infection, were excluded from the study.
The surgical specimens were evaluated by genitourinary pathologists. The Fuhrman grade system, TNM classification (7th edition from American Joint Committee, 2017) and histologic subtype (World Health Organization, 2016) were used for pathological result. The patients were divided into two groups according to the low and high T-stage and Fuhrman grade, as T1-T2 and T3-T4, G1-2 and G3-4, respectively. The platelet to lymphocyte ratio and neutrophil to lymphocyte ratio were compared between T1-T2 and T3-T4, G1-G2 and G3-G4. The receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic efficacy of PLR, NLR, platelet, neutrophil, and lymphocyte for advanced stage and high grade.
Distribution normality was analyzed with the Kolmogorov-Smirnov test. The normal distribution variable was compared with independent t test and the others were compared with Mann-Whitney U test. The chi-squared test was used for percentage values. Data were expressed as mean ± standard deviation for age, median for the others, and P < 0.05 as considered with statistical significance. Statistical analyses were performed using the demo version of MedCalc Statistical Software version 17.6 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2017).
Results
There were 271 patients in the study. Of these patients, 180 were male and 91 were female. The mean age of the patients was 59.37±11.62 years. Table 1 shows the characteristics and pathological results of the patients. The advanced stage (T3-T4) was reported in 64 patients (23.61%), and the Fuhrman grading system was reported in 258 patients: 48.83% had high grade (G3-G4). Table 2 shows the hematological parameters according to the grade and T stage classification. Both PLR and NLR were higher in patients with a more advanced stage and a higher grade than the others. The platelet was significantly higher in patients with T3-T4. The tumor size was correlated with T stage and Fuhrman grade.
Table
Table 1. The characteristics of the patients.
Table 1. The characteristics of the patients.
View larger version
Table
Table 2. The hematological parameters and patients’ characteristics according to the grade and T stage classification.
Table 2. The hematological parameters and patients’ characteristics according to the grade and T stage classification.
View larger version
The ROC analysis is shown in Figure 1. There was no significant difference between NLR and PLR to predict the stage and grade (P=0.07). The area under curve (AUC) was greater for PLR to predict the advanced stage than for the others. There was a significant difference between PLR and lymphocyte (P=0.001). The lymphocyte had the biggest AUC for advanced stage diagnosis (0.605), and a significant difference was detected between PLR and platelet (P=0.01). The AUC of the hematological parameters are seen in Table 3.
figure
Figure 1. The ROC of the parameters. ROC: receiver operating characteristic.
Table
Table 3. The AUC of the hematological parameters in advanced stage and high grade.
Table 3. The AUC of the hematological parameters in advanced stage and high grade.
View larger version
Discussion
The incidence of RCC has increased in the last three decades.10 The widespread use of radiologic imaging techniques may be one of the reasons for this increase.11 The other factors are environmental exposures, smoking, obesity, and changes in lifestyle. Surgery is the gold standard treatment for patients with localized disease, but 10%–60% of the patients develop recurrence after surgery.10 Although several prognostic factors have been reported for RCC, the stage and grade are the most important factors.11
In the pathophysiology of the cancer-associated systemic inflammation, the distribution of circulating inflammatory cells changes.12 The main change is neutrophilia with relative lymphocytopenia or thrombocytosis. Neutrophils secrete some cytokines including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, and vascular endothelial growth factor (VEGF), which is a proangiogenic factor.10 They also release reactive oxygen species, nitric oxide, and arginase.4 The neutrophils promote tumor growth and metastasis by remodeling the extracellular matrix and suppressing the T-cell response. Additionally, tumor cells produce immunosuppressive cytokines, which decrease the cytotoxic T lymphocytes.13 As a result, the decreased lymphocyte count causes suboptimal defense in the lymphocyte-mediated immune system against cancer. The platelets have a prominent role in cancer progression. They promote tumor growth and angiogenesis by VEGF cytokine.4 VEGF induces the formation of blood vessels and facilitates metastasis.14 Solid tumors produce IL-6, which contributes to the thrombocytosis. The IL-6 stimulates thrombopoietin that increases the platelet count in patients with malignancy.15 The other cytokines are IL-11, stem cell factor, and granulocyte-macrophage colony-stimulating factor.16
Some prognostic factors, such as NLR and PLR, which came from the blood cells, have been defined as valuable biomarkers to predict the prognosis in solid tumors.17 These biomarkers are cheap and easily acquired when compared with other markers such as C-reactive protein.18 The authors investigated the NLR in patients with metastatic RCC and found NLR>4 was independently associated with overall survival.19 The other study showed that high NLR (⩾1.7) was correlated both worse overall and disease-free survival in non-metastatic RCC.20 In addition, the authors found that preoperative NLR was associated with increased risk of death and all-cause mortality in patients with localized clear cell RCC.10 Most of the studies about NLR and RCC are about the prognosis, the clinical diagnosis and importance is limited in the literature. Otunctemur et al.3 reported that NLR was higher in patients with advanced stage and high grade (T3-4, G3-4) than the others. The authors found similar results; NLR value was significantly higher in patients with advanced disease and high grade of RCC.21 The current study showed that NLR was significantly higher in patients with advanced stage and high-grade disease (P<0.05).
In a meta-analysis; the authors reported that elevated PLR was associated with poor overall survival and disease-free survival in renal cancer.18 The other meta-analysis indicated that elevated PLR is an independent predictor of poor overall survival and progression-free survival in RCC.17 Baum et al. found that elevated PLR was associated with short survival.22 Dirikan et al., from Turkey, revealed that patients diagnosed with metastatic RCC with high PLR had shorter overall survival than the others without significant difference.23 In another study from the UK, the investigators found that high PLR was associated with high grade (G3), high T stage (T2+), and large tumor size (⩾3 cm).12 The authors reported that elevated PLR was associated with high grade (G3-4) and advanced T stage (T3-4) of RCC.21 In addition, PLR was found to be significantly increased in the advanced stage (III-IV) of ovarian cancer.5 The current study showed that elevated PLR was associated with high grade and advanced stage disease (P<0.05).
There are some limitations in the current study. The retrospective design, which is associated with selection bias and incomplete data collection, is the main limitation. Also, overall survival and cancer-specific survival was not evaluated. These limitations include a relatively large series of RCCs from Turkey regarding the clinical significance of PLR and NLR for the pathology of RCC.
In conclusion, the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio may predict the pathological outcome for patients with RCCs. Further studies are needed to understand the role of these ratios in the pathology of RCCs.
Authors’ Note
Selahattin Çalışkan is now affiliated with Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey.
Declaration of conflicting interest
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
References
1. Fukuda, H, Takagi, T, Kondo, T. Predictive value of inflammation based prognostic scores in patients with metastatic renal cell carcinoma treated with cytoreductive nephrectomy. Oncotarget 2018; 9: 14296–14305.
Google Scholar | Medline
2. Wang, X, Su, S, Guo, Y. The clinical use of the platelet to lymphocyte ratio and lymphocyte to monocyte ratio as prognostic factors in renal cell carcinoma: a systematic review and meta-analysis. Oncotarget 2017; 8: 84506–84514.
Google Scholar | Medline
3. Otunctemur, A, Dursun, M, Besiroğlu, H. Clinical significance of preoperative neutrophil to lymphocyte ratio in renal cell carcinoma. Int Braz J Urol 2016; 42: 678–684.
Google Scholar | Medline
4. Kemal, Y, Yucel, I, Ekiz, K. Elevated serum neutrophil to lymphocyte and platelet to lymphocyte ratios could be useful in lung cancer diagnosis. Asian Pac J Cancer Prev 2014; 15: 2651–2654.
Google Scholar | Medline
5. Kokcu, A, Kurtoglu, E, Celik, H. May the platelet to lymphocyte ratio be a prognostic factor for epithelial ovarian cancer? Asian Pac J Cancer Prev 2014; 15: 9781–9784.
Google Scholar | Medline
6. Walsh, SR, Cook, EJ, Goulder, F. Neutrophil lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 2005; 91: 181–184.
Google Scholar | Medline | ISI
7. Thavarama, T, Phaloprakarn, C, Tangjitgamol, S. Role of neutrophil to lymphocyte ratio as a prognostic indicator for epithelial ovarian cancer. J Med Assoc Thai 2011; 94: 871–877.
Google Scholar | Medline
8. Jankovich, M, Jankovichova, T, Ondrus, D. Neutrophil to lymphocyte ratio as a predictor of preoperative tumor staging in testicular germ cell tumors. Bratisl Med J 2017; 118: 510–512.
Google Scholar
9. Wojtas, AS, Lubas, A, Stec, R. Neutropil to lymphocyte ratio, platelet to lymphocyte ratio, C-reactive protein as new simple prognostic factors in patients with metastatic renal cell cancer treated with tyrosine kinase inhibitors: a systematic review and meta-analysis. Clin Genitourin Canc 2018; 16: 685–693.
Google Scholar
10. Viers, BR, Thompson, RH, Boorjan, SA. Preoperative neutrophil-lymphocyte ratio predicts death among patients with localized clear cell renal carcinoma undergoing nephrectomy. Urol Oncol-Semin Ori 2014; 32: 1277–1284.
Google Scholar | Medline
11. Seda, CJO, Salas, ASJ, Sanchez, CG. Thrombocytosis and hematocrit as prognostic factors in renal carcinoma. Arch Esp Urol 2011; 64: 883–890.
Google Scholar | Medline
12. Lee, SM, Russell, A, Hellawell, G. Predictive value of pretreatment inflammation based prognostic scores (neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and lymphocyte to monocyte ratio) for invasive bladder carcinoma. Korean J Urol 2015; 56: 745–799.
Google Scholar
13. Hu, K, Lou, L, Ye, J. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open 2015; 5: e006404.
Google Scholar | Medline | ISI
14. Kilincalp, S, Çoban, Ş, Akınc, H. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume as potential biomarkers for early detection and monitoring of colorectal adenocarcinoma. Eur J Cancer Prev 2015; 24: 328–333.
Google Scholar | Medline
15. Templeton, AJ, Ace, O, McNamara, MG. Prognostic role of platelet to lymphocyte ratio in solid tumors. A systematic review and meta-analysis. Canc Epidemiol Biomarkers Prev 2014; 23: 1204–1212.
Google Scholar | Medline | ISI
16. Choi, JY, Ko, YH, Song, PH. Clinical significance of preoperative thrombocytosis in patients who underwent radical nephrectomy for nonmetastatic renal cell carcinoma. Investig Clin Urol 2016; 57: 324–329.
Google Scholar | Medline
17. Wang, Z, Peng, S, Wang, A. Platelet lymphocyte ratio acts as an independent predictor of prognosis in patients with renal cell carcinoma. Clin Chim Acta 2018; 480: 166–172.
Google Scholar | Medline
18. Luo, Y, She, D, Xiong, H. Pretreatment neutrophil to lymphocyte ratio as a prognostic predictor of urologic tumors. Medicine (Baltimore) 2015; 94: e1670.
Google Scholar | Medline
19. Baum, YS, Patil, D, Huang, JH. Elevated preoperative neutrophil to lymphocyte ratio may be associated with decreased overall survival in patients with metastatic clear cell renal cell carcinoma undergoing cytoreductive nephrectomy. Asian J Urol 2015; 3: 20–25.
Google Scholar | Medline
20. Wen, RM, Zhang, YJ, Ma, S. Preoperative neutrophil to lymphocyte ratio as prognostic factor in patients with non-metastatic renal cell carcinoma. Asian Pac J Cancer Prev 2015; 16: 3703–3708.
Google Scholar | Medline
21. Peng, D, He, Z-s, Li, X-s. Prognostic value of inflammatory and nutritional scores in renal cell carcinoma after nephrectomy. Clin Genitourin Canc 2017; 15: 582–590.
Google Scholar | Medline
22. Wang, J, Liu, Y, Zhang, N. Prognostic role of pretreatment platelet to lymphocyte ratio in urologic cancer. Oncotarget 2017; 8: 70874–70882.
Google Scholar | Medline
23. Dirican, A, Kucukzeybek, Y, Somali, I. The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma. JBUON 2013; 18: 413–419.
Google Scholar
View Abstract
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου