본문 바로가기
KERD
논문KCI 등재

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

정준철|정동준|김형철|이문수|진수지|안태성|배상호|백무준|정해일|지상희
대한암학회 (Korean Cancer Association)|2017.01|Cancer Research and Treatment|제49권 제1호|pp. 246-254

1

조회

0

다운로드

3

인용

0

참고문헌

키워드

Hepatocellular carcinomaPrognosisProgrammed cell death 1Programmed cell death 1 ligand
주제분류의학일반

초록

Purpose Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC. Materials and Methods Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis. Results The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034). Conclusion The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted. Key

Abstract

Purpose Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC. Materials and Methods Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis. Results The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034). Conclusion The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted. Key

참고문헌 (23)

  1. El-Serag HB, "Hepatocellular carcinoma", N Engl J Med, 365, pp.1118~1127 (2011)
  2. Vilarinho S, "Therapeutic strategies for hepatocellular carcinoma : new advances and challenges", Curr Treat Options Gastroenterol, 13, pp.219~234 (2015)
  3. Sangro B, "Immunotherapy of hepatocellular carcinoma", Hepat Oncol, 1, pp.433~446 (2014)
  4. Ohaegbulam KC, "Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway", Trends Mol Med, 21, pp.24~33 (2015)
  5. Ma H, "Progress of immunotherapy for hepatocellular carcinoma", Immunogastroenterology, 2, pp.167~172 (2013)
  6. Qing Y, "Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer", Drug Des Devel Ther, 9, pp.901~909 (2015)
  7. Pan ZK, "Clinicopathological and prognostic significance of programmed cell death ligand1(PD-L1)expression in patients with non-small cell lung cancer : a meta-analysis", J Thorac Dis, 7, pp.462~470 (2015)
  8. Tentori L, "Challenging resistance mechanisms to therapies for metastatic melanoma", Trends Pharmacol Sci, 34, pp.656~666 (2013)
  9. Thompson RH, "PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma", Clin Cancer Res, 13, pp.1757~1761 (2007)
  10. Nomi T, "Clinical significance and therapeutic potential of the programmed death-1 ligand", programmed death-1 pathway in human pancreatic cancer, 2007, pp.13, 2151~2157
  11. Hamanishi J, "Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer", Proc Natl Acad Sci U S A, 104, pp.3360~3365 (2007)
  12. McDermott DF, "PD-1 as a potential target in cancer therapy", Cancer Med, 2, pp.662~673 (2013)
  13. Gao Q, "Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma", Clin Cancer Res, 15, pp.971~979 (2009)
  14. Wang BJ, "Immunostaining of PD-1", PD-Ls in liver tissues of patients with hepatitis and hepatocellular carcinoma, 2011, pp.17, 3322~3329
  15. Zeng Z, "Upregulation of circulating PD-L1", PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma, 2011, pp.6, e23621~
  16. He L, "Blockade of B7-H1 with sPD-1 improves immunity against murine hepatocarcinoma", Anticancer Res, 25, pp.3309~3313 (2005)
  17. Rozali EN, "Programmed death ligand 2 in cancer-induced immune suppression", Clin Dev Immunol, 2012, pp.656340~ (2012)
  18. Huber S, "Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2", Blood, 116, pp.3311~3320 (2010)
  19. Hamid O, "Safety and tumor responses with lambrolizumab(anti-PD-1)in melanoma", N Engl J Med, 369, pp.134~144 (2013)
  20. Topalian SL, "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer", N Engl J Med, 366, pp.2443~2454 (2012)
  21. Pardoll DM, "The blockade of immune checkpoints in cancer immunotherapy", Nat Rev Cancer, 12, pp.252~264 (2012)
  22. Tiegs G, "Immune tolerance : what is unique about the l iver", J Autoimmun, 34, pp.1~6 (2010)
  23. Sangro B, "A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C", J Hepatol, 59, pp.81~88 (2013)

이 간행물의 다른 논문 (29건)

How Can We Treat Cancer Disease Not Cancer Cells?이호영, 김우영, 서지혜, 이수재, 김규원pp. 1-9A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors김혜영, 이건국, 남병호, 한혜선, 정진아, 이진수, 김상위, 민영주, 이기형, 한지연, 조은경, 이영주, 이수현pp. 10-19Minimally Invasive Stereotactical Radio-ablation of Adrenal Metastases as an Alternative to SurgeryPietro Mancosu, Pierina Navarria, Stefano Tomatis, Luca Cozzi, Marta Scorsetti, Ciro Franzese, Davide Franceschini, Giuseppe D’Agostino, Tiziana Comito, Fiorenza De Rose, Antonella Fogliatapp. 20-28Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study기영준, 최진아, 문선미, 고민정, 서영석, 박찬미, 김미숙, 김효정pp. 29-36Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer장세진, 천성민, 김규표, 김달용, 김지훈, 이재련, 김태원, 김정은, 홍용상pp. 37-43
원문 보기