Tumor Biology

, Volume 36, Issue 4, pp 2263–2269 | Cite as

Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma

  • Xing Li
  • Zhan-Hong Chen
  • Yan-Fang Xing
  • Tian-Tian Wang
  • Dong-Hao Wu
  • Jing-Yun Wen
  • Jie Chen
  • Qu Lin
  • Min Dong
  • Li Wei
  • Dan-Yun Ruan
  • Ze-Xiao Lin
  • Xiang-Yuan Wu
  • Xiao-Kun Ma
Research Article

Abstract

The platelet count, as an inflammation marker, is involved in the progress of tumor invasion. However, the prognostic value of platelet counts and the platelet-to-lymphocyte ratio (PLR) has not been investigated in patients with advanced hepatocellular carcinoma (HCC). This study aimed to determine the prognostic value of platelet counts and PLR in HCC patients. A total of 243 ethnic Chinese advanced HCC patients from two major hospitals, not receiving systemic sorafenib, were analyzed retrospectively. The prognostic value of differential blood cell counts and PLR for overall survival (OS) was determined by integrating the Cancer of the Liver Italian Program (CLIP) score system and model for end-stage liver disease by using a stepwise model of multivariate Cox regression. The Kaplan–Meier method and receiver operating characteristic (ROC) curves were utilized accordingly. PLR was confirmed to be an independent predictor for OS (p < 0.01), while the remaining parameters had no predictive value. Then, advanced HCC patients were dichotomized into two groups based on the PLR value (≤111.23 or >111.23), according to ROC analysis. Patients with a high PLR had a lower 3-month survival rate (37.6 vs. 57.6 %) compared with patients with a low PLR. PLR was associated with aggressive malignant behavior, characterized by distant metastasis and portal vein thrombosis. Additionally, PLR was not associated with the CLIP score and Child–Pugh grade. PLR was identified as an independent prognostic factor for advanced HCC patients not receiving systemic sorafenib; the predictive ability of PLR partially relies on its association with the aggressive nature of HCC.

Keywords

Platelet–lymphocyte ratio Hepatocellular carcinoma Prognosis Blood cell counts Score system 

Notes

Conflicts of interest

None

Financial support

This work was supported by grants from the National Natural Science Foundation of China (No. 81372374), the Combination Project of Production, Education and Research from Guangdong Province and Ministry of Education (No. 2012B091100460), and the Science and Technology Planning Project of Guangdong Province 2011B031800076 (to Q. Lin), 2011B031800014 (to M. Dong) and 2012B031800259 (to J. Wen).

References

  1. 1.
    Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63:844–55.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yau T, Yao TJ, Chan P, Ng K, Fan ST, Poon RT. A new prognostic score system in patients with advanced hepatocellular carcinoma not amendable to locoregional therapy: implication for patient selection in systemic therapy trials. Cancer. 2008;113:2742–51.CrossRefPubMedGoogle Scholar
  3. 3.
    Li X, Dong M, Lin Q, Chen ZH, Ma XK, Xing YF, et al. Comparison of current staging systems for advanced hepatocellular carcinoma not amendable to locoregional therapy as inclusion criteria for clinical trials. Asia Pac J Clin Oncol. 2013;9:86–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Bugada D, Allegri M, Lavand’homme P, De Kock M, Fanelli G. Inflammation-based scores: a new method for patient-targeted strategies and improved perioperative outcome in cancer patients. Biomed Res Int. 2014;2014:142425.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science. 2013;339:286–91.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Nozoe T, Iguchi T, Adachi E, Matsukuma A, Ezaki T. Preoperative elevation of serum c-reactive protein as an independent prognostic indicator for gastric cancer. Surg Today. 2011;41:510–3.CrossRefPubMedGoogle Scholar
  7. 7.
    Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.CrossRefPubMedGoogle Scholar
  8. 8.
    Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via p2y2 receptor. Cancer Cell. 2013;24:130–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Grosse-Steffen T, Giese T, Giese N, Longerich T, Schirmacher P, Hansch GM, et al. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase. Clin Dev Immunol. 2012;2012:720768.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Llovet JM, Moitinho E, Sala M, Bataller R, Rodriguez-Iglesias P, Castells A, et al. Prevalence and prognostic value of hepatocellular carcinoma in cirrhotic patients presenting with spontaneous bacterial peritonitis. J Hepatol. 2000;33:423–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11:123–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Buergy D, Wenz F, Groden C, Brockmann MA. Tumor-platelet interaction in solid tumors. Int J Cancer. 2012;130:2747–60.CrossRefPubMedGoogle Scholar
  13. 13.
    Unal D, Eroglu C, Kurtul N, Oguz A, Tasdemir A. Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis? Asian Pac J Cancer Prev. 2013;14:5237–42.CrossRefPubMedGoogle Scholar
  14. 14.
    Feng JF, Huang Y, Zhao Q, Chen QX. Clinical significance of preoperative neutrophil lymphocyte ratio versus platelet lymphocyte ratio in patients with small cell carcinoma of the esophagus. Sci World J. 2013;2013:504365.Google Scholar
  15. 15.
    Ertas IE, Gungorduk K, Akman L, Ozdemir A, Terek MC, Ozsaran A, et al. Can preoperative neutrophil: lymphocyte and platelet: lymphocyte ratios be used as predictive markers for lymph node metastasis in squamous cell carcinoma of the vulva? Eur J Obstet Gynecol Reprod Biol. 2013;171:138–42.CrossRefPubMedGoogle Scholar
  16. 16.
    Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol. 2012;23:265–73.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Szkandera J, Pichler M, Absenger G, Stotz M, Arminger F, Weissmueller M, et al. The elevated preoperative platelet to lymphocyte ratio predicts decreased time to recurrence in colon cancer patients. Am J Surg. 2014;208(2):210–4.CrossRefPubMedGoogle Scholar
  18. 18.
    He W, Yin C, Guo G, Jiang C, Wang F, Qiu H, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol. 2013;30:439.CrossRefPubMedGoogle Scholar
  19. 19.
    Lee S, Oh SY, Kim SH, Lee JH, Kim MC, Kim KH, et al. Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with folfox chemotherapy. BMC Cancer. 2013;13:350.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Karpatkin S, Pearlstein E, Ambrogio C, Coller BS. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest. 1988;81:1012–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Sierko E, Wojtukiewicz MZ. Platelets and angiogenesis in malignancy. Semin Thromb Hemost. 2004;30:95–108.CrossRefPubMedGoogle Scholar
  23. 23.
    Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20:576–90.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Labelle M, Begum S, Hynes RO. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A. 2014;111(30):E3053–61.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kobayashi N, Hiraoka N, Yamagami W, Ojima H, Kanai Y, Kosuge T, et al. Foxp3+ regulatory t cells affect the development and progression of hepatocarcinogenesis. Clin Cancer Res. 2007;13:902–11.CrossRefPubMedGoogle Scholar
  26. 26.
    Pinato DJ, Stebbing J, Ishizuka M, Khan SA, Wasan HS, North BV, et al. A novel and validated prognostic index in hepatocellular carcinoma: the inflammation based index (IBI). J Hepatol. 2012;57:1013–20.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xing Li
    • 1
  • Zhan-Hong Chen
    • 1
  • Yan-Fang Xing
    • 2
  • Tian-Tian Wang
    • 1
  • Dong-Hao Wu
    • 1
  • Jing-Yun Wen
    • 1
  • Jie Chen
    • 1
  • Qu Lin
    • 1
  • Min Dong
    • 1
  • Li Wei
    • 1
  • Dan-Yun Ruan
    • 1
  • Ze-Xiao Lin
    • 1
  • Xiang-Yuan Wu
    • 1
  • Xiao-Kun Ma
    • 1
  1. 1.Department of Medical OncologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  2. 2.Department of NephrologyThe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

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