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Tae Sung Ahn 1 Article
Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma
Hae Il Jung, Dongjun Jeong, Sanghee Ji, Tae Sung Ahn, Sang Ho Bae, Susie Chin, Jun Chul Chung, Hyung Chul Kim, Moon Soo Lee, Moo-Jun Baek
Cancer Res Treat. 2017;49(1):246-254.   Published online July 7, 2016
DOI: https://doi.org/10.4143/crt.2016.066
AbstractAbstract PDFPubReaderePub
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.

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    International Immunopharmacology.2020; 87: 106832.     CrossRef
  • Development and Validation of a Novel 8 Immune Gene Prognostic Signature Based on the Immune Expression Profile for Hepatocellular Carcinoma


    Dafeng Xu, Yu Wang, Kailun Zhou, Jincai Wu, Zhensheng Zhang, Jiachao Zhang, Zhiwei Yu, Luzheng Liu, Xiangmei Liu, Bidan Li, Jinfang Zheng
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    Aging.2020; 12(3): 3053.     CrossRef
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  • Prognostic and clinicopathological utility of PD-L2 expression in patients with digestive system cancers: A meta-analysis
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    Christo Kole, Nikolaos Charalampakis, Sergios Tsakatikas, Michail Vailas, Dimitrios Moris, Efthymios Gkotsis, Stylianos Kykalos, Michalis V. Karamouzis, Dimitrios Schizas
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    Piera Federico, Angelica Petrillo, Pasqualina Giordano, Davide Bosso, Antonietta Fabbrocini, Margaret Ottaviano, Mario Rosanova, Antonia Silvestri, Andrea Tufo, Antonio Cozzolino, Bruno Daniele
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  • Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy
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  • Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
    Qiu-Ju Sheng, Wen-Yue Tian, Xiao-Guang Dou, Chong Zhang, Yan-Wei Li, Chao Han, Yao-Xin Fan, Ping-Ping Lai, Yang Ding
    World Journal of Gastrointestinal Oncology.2020; 12(11): 1255.     CrossRef
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    F1000Research.2020; 9: 732.     CrossRef
  • Comprehensive Assessment of PD-L1 and PD-L2 Dysregulation in Gastrointestinal Cancers
    Qijie Zhao, Jinan Guo, Yueshui Zhao, Jing Shen, Parham Jabbarzadeh Kaboli, Shixin Xiang, Fukuan Du, Xu Wu, Mingxing Li, Lin Wan, Xiang Li, Qinglian Wen, Jing Li, Chang Zou, Zhangang Xiao
    Epigenomics.2020; 12(24): 2155.     CrossRef
  • PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer
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    Journal of Translational Medicine.2020;[Epub]     CrossRef
  • PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome
    Lingyu Tian, Jiaqiang Ma, Lijie Ma, Bohao Zheng, Longzi Liu, Danjun Song, Yining Wang, Zhao Zhang, Qiang Gao, Kang Song, Xiaoying Wang
    World Journal of Surgical Oncology.2020;[Epub]     CrossRef
  • Increased Expression of Programmed Death Ligand 1 in Hepatocellular Carcinoma of Patients with Hepatitis B Virus Pre-S2 Mutant


    Chiao-Fang Teng, Tsai-Chung Li, Ting Wang, Tzu-Hua Wu, John Wang, Han-Chieh Wu, Woei-Cherng Shyu, Ih-Jen Su, Long-Bin Jeng
    Journal of Hepatocellular Carcinoma.2020; Volume 7: 385.     CrossRef
  • Assessment of Current Gene Therapy Practices in Hepatocellular Carcinoma
    Bryan Mckiver, Mohamad Imad Damaj, Devanand Sarkar
    Gastrointestinal Disorders.2020; 2(4): 469.     CrossRef
  • Association between Genetic and Immunological Background of Hepatocellular Carcinoma and Expression of Programmed Cell Death-1
    Naoshi Nishida, Kazuko Sakai, Masahiro Morita, Tomoko Aoki, Masahiro Takita, Satoru Hagiwara, Yoriaki Komeda, Mamoru Takenaka, Yasunori Minami, Hiroshi Ida, Kazuomi Ueshima, Kazuto Nishio, Masatoshi Kudo
    Liver Cancer.2020; 9(4): 426.     CrossRef
  • Immune Checkpoint Inhibitors in Hepatocellular Cancer: Current Understanding on Mechanisms of Resistance and Biomarkers of Response to Treatment
    Amblessed E. Onuma, Hongji Zhang, Hai Huang, Terence M. Williams, Anne Noonan, Allan Tsung
    Gene Expression.2020; 20(1): 53.     CrossRef
  • Pre-treatment serum levels of soluble programmed cell death-ligand 1 predict prognosis in patients with hepatitis B-related hepatocellular carcinoma
    Xue Han, Yang-kui Gu, Shao-long Li, Hao Chen, Min-shan Chen, Qing-qing Cai, Han-xia Deng, Meng-xuan Zuo, Jin-hua Huang
    Journal of Cancer Research and Clinical Oncology.2019; 145(2): 303.     CrossRef
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    T. Mocan, Z. Sparchez, R. Craciun, C. N. Bora, D. C. Leucuta
    Clinical and Translational Oncology.2019; 21(6): 702.     CrossRef
  • Prognostic significance of PD‐L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD‐L1 expression profile
    Manuel Weber, Falk Wehrhan, Christoph Baran, Abbas Agaimy, Maike Büttner‐Herold, Marco Kesting, Jutta Ries
    Cancer Medicine.2019; 8(3): 1124.     CrossRef
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    Cancer Cell International.2019;[Epub]     CrossRef
  • Prognostic value of programed death ligand-1 and ligand-2 co-expression in salivary gland carcinomas
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    Oral Oncology.2019; 90: 30.     CrossRef
  • Observational Study of PD-L1, TGF-β, and Immune Cell Infiltrates in Hepatocellular Carcinoma
    Christian Ihling, Bartholomew Naughton, Yue Zhang, P. Alexander Rolfe, Eveline Frick-Krieger, Luigi M. Terracciano, Isabelle Dussault
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  • Clinicopathological, Immune and Molecular Correlates of PD-L2 Methylation in Gastric Adenocarcinomas
    Philipp Lingohr, Jonas Dohmen, Alexander Semaan, Vittorio Branchi, Jörn Dietrich, Friedrich Bootz, Jörg C Kalff, Hanno Matthaei, Dimo Dietrich
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  • Serum PD-1 Levels Change with Immunotherapy Response but Do Not Predict Prognosis in Patients with Hepatocellular Carcinoma
    Hye Won Lee, Kyung Joo Cho, Soon Young Shin, Ha Yan Kim, Eun Ju Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han
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    American Journal of Transplantation.2018; 18(5): 1206.     CrossRef
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  • Immune checkpoints and their inhibition in cancer and infectious diseases
    Lydia Dyck, Kingston H.G. Mills
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  • Expression and prognostic significance of programmed death protein 1 and programmed death ligand‐1, and cytotoxic T lymphocyte‐associated molecule‐4 in hepatocellular carcinoma
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  • PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy
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  • PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer
    Dagmar Kollmann, Thomas Schweiger, Stefan Schwarz, Desislava Ignatova, Yun-Tsan Chang, Gerrit Lewik, Sebastian F. Schoppmann, Wolfram Hoetzenecker, Walter Klepetko, Emmanuella Guenova, Konrad Hoetzenecker
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  • PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer
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