The Relationship Between Thrombocyte Lymphocyte Ratio With Tumor Morphology and Alpha Fetoprotein in Patients with Hepatocellular Carcinoma

Abstract

Introduction: The aim of this study was to investigate the relationship between platelet lymphocyte ratio (PLR) and morphological and clinicopathological features of tumor in patients with hepatocellular carcinoma (HCC). Method: Patients diagnosed with HCC by imaging methods (dynamic-triphasic CT and dynamic-MR) and/or tissue sampling (biopsy, resectionor explant) were retrospectively reviewed. Demographic characteristics, etiology, arising from cirrhotic or non-cirrhotic, morphological characteristics of the tumor (tumor diameter, focality, vascular invasion) and; complete blood count, alpha-fetoprotein (AFP), platelet and lymphocyte counts were calculated at the time of diagnosis. Findings: A total of 223 patients were included in the present study. Of the 223 patients, 185 (82.9%) were male and 38 (17.1%) were female. There was a positive correlation between PLR and AFP (p = 0.05). PLR was significantly higher in patients with portal vein invasion (p = 0.001). PLR values were significantly higher in patients with solitary lesions than those with infiltrative lesions. PLR values were significantly higher in patients with infiltrative tumors than patients with two or more solitary lesions (p = 0.001). There was a positive correlation between maximal tumor diameter (MTD) and PLR in patients with non-infiltrative type tumor (p=0.01). Results: PLR is a cheap and easily applicable marker. It is positively correlated with poor prognostic factors such as vascular invasion, AFP and MTD. PLR can also be used as an additional prognostic biomarker to assess tumor aggressiveness.



Giriş: Bu çalışmada, hepatosellüler karsinom (HCC) tanılı hastalarda platelet lenfosit oranı (PLR) ile tümörün morfolojik ve klinikopatolojik özellikleri arasındaki ilişkinin belirlenmesi amaçlandı. Yöntem: Görüntüleme yöntemleri (dinamik-trifazik CT ve dinamik-MR) ve/veya doku örneklemesi (biyopsi, rezeksiyon veya eksplant) ile HCC tanısı alan hastalar retrospektif olarak incelendi. Hastaların demografik özellikleri, etyolojisi, sirotik veya non-sirotik zeminde gelişmesi, tümörün morfolojik özellikleri (tümör çapı, fokalitesi, vasküler invazyon), tanı anındaki tam kan sayımı, Alfa-fetoprotein (AFP), trombosit ve lenfosit değerleri hesaplandı. Bulgular: Çalışmaya 223 hasta dahil edildi. 223 hastanın 185’i (%82,9) erkek , 38’i (%17,1) kadındı. PLR ile AFP arasında pozitif korelasyon (p=0,05) saptanırken, portal ven invazyonu olan hastalarda PLR’nin istatistiksel olarak anlamlı derecede yüksek olduğu görüldü (p=0.001). PLR değeri soliter lezyonu olanlarda infiltratif gruptan anlamlı olarak fazlaydı. PLR değeri infiltratif grupta ise iki veya daha fazla nodulü olan gruba oranla istatistiksel olarak anlamlı düzeyde fazlaydı (p=0,001). İnfiltratif tip tümör dışındaki hastalarda maksimal tümör çapı (MTD) arttıkça PLR’nin de istatistiki olarak anlamlı biçimde arttığı izlendi (p=0,01). Sonuç: PLR, ucuz ve kolay ulaşılabilir bir belirteç olup AFP, vasküler invazyon ve MTD gibi kötü prognostik faktörlerle pozitif korele olarak değişmektedir. Tümörün agresifliğini değerlendirmek için PLR de ek bir prognostik biyomarker olarak kullanılabilir. 

Keywords

• Trombosit-lenfosit oranı,hepatosellüler kanser,prognosis.

Hepatosellüler Kanser Tanılı Hastalarda Trombosit Lenfosit Orani’nin Tümör Morfolojisi ve Alfa Fetoprotein ile İlişkisi

Abstract

Giriş: Bu çalışmada hepatocellüler karsinom (HCC) tanılı hastalarda platelet lenfosit oranı (PLO) ile tümörün morfolojik ve klinikopatolojik özellikleri arasındaki ilişkinin belirlenmesi amaçlandı. Yöntem: Görüntüleme yöntemleri (dinamik-trifazik CT ve dinamik-MR) ve/ve ya doku örneklemesi (biyopsi, rezeksiyon veya eksplant) ile HCC tanısı alan hastalar retrospektif olarak incelendi. Hastaların demografik özellikleri, etyolojisi, sirotik veya non-sirotik zeminde gelişmesi, tümörün morfolojik özellikleri (tumor çapı, fokalitesi, vasküler invazyon), tanı anındaki tam kan sayımı, Alfa-fetoprotein, trombosit ve lenfosit değerleri hesaplandı. Bulgular: Çalışmaya 223 hasta dahil edildi. 223 hastanın 185 (%82,9)’i erkek , 38 (%17,1)’i kadındı. PLO ile AFP arasında pozitif korelasyon (p=0,05) saptanırken, portal ven invazyonu olan hastalarda PLO’nun istatistiksel olarak anlamlı derecede yüksek olduğu görüldü (p=0.001). PLO değeri soliter lezyonu olanlarda infiltratif gruptan anlamlı olarak fazlaydı. PLO değeri infiltratif grupta ise iki veya daha fazla nodulü olan gruptan istatistiksel anlamlı olarak fazlaydı (p=0,001). İnfiltratif tip tümör dışındaki hastalarda maksimal tümör çapı (MTD) arttıkça PLR’nin de istatistiki olarak anlamlı derece arttığı izlendi (p=0,01). Sonuç: PLO; ucuz ve kolay ulaşılabilir bir belirteç olup; AFP , vasküler invazyon ve MTD gibi kötü prognostik faktörlerle pozitif korele olarak değişmektedir.Tümör agresifliği değerlendirmek için PLO da ek bir prognostik biyomarker olarak kullanılabilir.

Keywords

• Trombosit-lenfosit oranı,hepatosellüler kanser,prognoz

References

1. 1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics.. CA Cancer J Clin. 2015; 65:87-108.
2. 2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012; 379:1245-55.
3. 3. Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Yet al. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol. 2010; 28:3994-4005.
4. 4. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140:883-99.
5. 5. Grange, J. M., Krone, B. , Mastrangelo, G. Infection, inflammation and cancer. International journal of cancer . 2011; 128 :2240–2250
6. 6. Proctor, M. J. et al. A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. European journal of cancer . 1990; 47:2633–2641
7. 7. Facciorusso A, Prete VD, Antonino M, Neve V, Crucinio N, Leo AD et al. Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation. J Gastroenterol Hepatol. 2014; 29:1905-1910.
8. 8. Lee S, Song A, Eo W. Serum Ferritin as a Prognostic Biomarker for Survival in Relapsed or Refractory Metastatic Colorectal Cancer. J Cancer. 2016; 7:957-64.

9. 9. Chen Y, Chen K, Xiao X, Nie Y, Qu S, Gong C et al. Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients: a retrospective study. BMC Cancer. 2016; 16:2352-2358.
10. 10. Wu SJ, Lin YX, Ye H, Li FY, Xiong XZ, Cheng NS. Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy. J Surg Oncol. 2016; 114:202-10.
11. 11. Gu X, Gao XS, Cui M, Xie M, Peng C, Bai Y et al. Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer. Oncotarget. 2016; 7:49878-49887.
12. 12. Matsuzaki K, Murata M, Yoshida K, Sekimoto G, Uemura Y, Sakaida N et al. Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology. 2007; 46:48-57.
13. 13. Fan W, Zhang Y, Wang Y, Yao X, Yang J, Li J.Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization. PloS one.2015;10:e0119312.
14. 14. Xue TC, Jia QA, Ge NL, Zhang BH, Wang YH, Ren ZG, et al. Theplatelet-to-lymphocyte ratio predicts poor survival in patients with hugehepatocellular carcinoma that received transarterial chemoembolization. TumourBiol. 2015 ;36 :6045-6051.
15. 15. Lai, Q., Lerut, J. Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer. Transplant international: official journal of the European Society for Organ Transplantation . 2014;27 : 32–41.
16. 16. Goh BK, Kam JH, Lee SY, Chan CY, Allen JC, Jeyaraj P, Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and prognostic nutrition index as preoperative predictors of early mortality after liver resection for huge (>/=10 cm) hepatocellular carcinoma. J Surg Oncol. 2016; 113:621-627.
17. 17. 17. Ji F, Liang Y, Fu SJ, Guo ZY, Shu M, Shen SL, Et al. A novel and accurate predictor of survival for patients with hepatocellular carcinoma after surgical resection: the neutrophil to lymphocyte ratio (NLR) combined with the aspartate aminotransferase/platelet count ratio index (APRI). BMC Cancer. 2016; 16:137.
18. 18. Tian XC, Liu XL, Zeng FR, Chen Z, Wu DH. Platelet-to-lymphocyte ratio acts as an independent risk factor for patients with hepatitis B virus-related hepatocellular carcinoma who received transarterial chemoembolization. Eur Rev Med Pharmacol Sci. 2016; 20:2302-2309.
19. 19. Lai Q, Castro Santa E, Rico Juri JM, Pinheiro RS, Lerut J. Neutrophil and platelet-to-lymphocyte ratio as new predictors of dropout and recurrence after liver transplantation for hepatocellular cancer. Transpl Int. 2014; 27:32-41.
20. 20. Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem. 1988; 263:7646-7654.
21. 21. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011; 11:123-134.
22. 22. Banks RE, Forbes MA, Kinsey SE, Stanley A, Ingham E, Walters C, et al. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer. 1998; 77:956-964.
23. 23. Man YG, Stojadinovic A, Mason J, Avital I, Bilchik A, Bruecher B, et al. Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories. J Cancer. 2013; 4:84-95.
24. 24. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–867.
25. 25. Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem. 1988;263:7646–7654.
26. 26. Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11:123–134.
27. 27. Banks RE, Forbes MA, Kinsey SE, Stanley A, Ingham E, Walters C, et al. Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets: significance for VEGF measurements and cancer biology. Br J Cancer. 1998;77:956–964.
28. 28. Man YG, Stojadinovic A, Mason J, Avital I, Bilchik A, Bruecher B, et al. Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories. J Cancer. 2013;4:84–95.
29. 29. Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O’Reilly DS, et al. A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer .2011; 47: 2633-2641.
30. 30. Xue TC, Jia QA, Ge NL, Zhang BH, Wang YH, Ren ZG, et al. The platelet-to-lymphocyte ratio predicts poor survival in patients with huge hepatocellular carcinoma that received transarterial chemoembolization. Tumour Biol. 2015; 36: 6045-6051.
31. 31. Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011; 29: 610-618.
32. 32. Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost 2011; 9: 237-249.
33. 33. Senzel L, Gnatenko DV, Bahou WF. The platelet proteome. Curr Opin Hematol. 2009; 16: 329-333.
34. 34. Tang X, Huang J, Xiong H, Zhang K, Chen C, Wei X,et al. Anti-tumor effects of the Polysaccharide isolated from tarphochlamys affinis in H22 tumor-bearing mice. Cell Physiol Biochem . 2016; 39: 1040-1050.
35. 35. Wang Y, Liu T, Tang W, Deng B, Chen Y, Zhu J, et al. Hepatocellular carcinoma cells induce regulatory T cells and lead to poor prognosis via production of transforming growth factor-β1. Cell Physiol Biochem . 2016; 38: 306-318.
36. 36. Shen Y, Wei Y, Wang Z, Jing Y, He H, Yuan J, et al. TGF-β regulates hepatocellular carcinoma progression by inducing Treg cell polarization. Cell Physiol Biochem. 2015; 35: 1623-1632.
37. 37. Unitt E, Marshall A, Gelson W, Rushbrook SM, Davies S, Vowler SL, et al.Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation. J Hepatol. 2006; 45: 246-253.