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PMID: 30761122 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

LAYN Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric and Colon Cancers.

Frontiers in immunology ·Vol. 10 ·2019-00-00 ·Pages 6

Pan JH, Zhou H, Cooper L, Huang JL, Zhu SB, Zhao XX, Ding H, Pan YL, Rong L

Abstract

Background: Layilin (LAYN) is a critical gene that regulates T cell function. However, the correlations of LAYN to prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear. Methods: LAYN expression was analyzed via the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We evaluated the influence of LAYN on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between LAYN and cancer immune infiltrates was investigated via TIMER. In addition, correlations between LAYN expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA. Results: A cohort (GSE17536) of colorectal cancer patients showed that high LAYN expression was associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In addition, high LAYN expression was significantly correlated with poor OS and progression-free survival (PFS) in gastric cancers (OS HR = 1.97, P = 3.6e-10; PFS HR = 2.12, P = 2.3e-10). Moreover, LAYN significantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA). Specifically, high LAYN expression was correlated with worse OS and PFS in stage 2 to 4 but not stage 1 and stage N0 gastric cancer patients (P = 0.28, 0.34; P = 0.073, 0.092). LAYN expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in colon adenocarcinoma (COAD) and stomach adenocarcinoma (STAD). LAYN expression showed strong correlations with diverse immune marker sets in COAD and STAD. Conclusions: These findings suggest that LAYN is correlated with prognosis and immune infiltrating levels of, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in colon and gastric cancer patients. In addition, LAYN expression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest that LAYN can be used as a prognostic biomarker for determining prognosis and immune infiltration in gastric and colon cancers.

Keywords
LAYN colon cancer gastric cancer lymphocytes prognosis tumor-infiltrating
MeSH Terms
Biomarkers, Tumor Colonic Neoplasms/etiology,mortality,pathology Databases, Factual Dendritic Cells/immunology,metabolism,pathology Female Gene Expression Profiling Humans Kaplan-Meier Estimate Lectins, C-Type/genetics,metabolism Lymphocyte Subsets/immunology,metabolism Lymphocytes, Tumor-Infiltrating/immunology,metabolism,pathology Macrophages/immunology,metabolism,pathology Male Neoplasm Metastasis Neoplasm Staging Prognosis Survival Analysis Tumor Microenvironment/immunology
Chemicals
Biomarkers, Tumor LAYN protein, human Lectins, C-Type
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Pan Jing-Hua
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China. | Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Zhou Hong
Department of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Cooper Laura
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Huang Jin-Lian
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Zhu Sheng-Bin
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Zhao Xiao-Xu
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Ding Hui
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Pan Yun-Long
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Rong Lijun
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
References (43)
43 references, click to expand
  1. Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma.
    Clin Cancer Res. 2010 Mar 1;16(5):1662-72 PMID: 20179239
  2. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses.
    Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102 PMID: 28407145
  3. TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.
    Cancer Res. 2017 Nov 1;77(21):e108-e110 PMID: 29092952
  4. PrognoScan: a new database for meta-analysis of the prognostic value of genes.
    BMC Med Genomics. 2009 Apr 24;2:18 PMID: 19393097
  5. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients.
    Breast Cancer Res Treat. 2016 Dec;160(3):439-446 PMID: 27744485
  6. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer.
    Cancer Immun. 2007 Feb 21;7:4 PMID: 17311363
  7. Pembrolizumab for the treatment of non-small-cell lung cancer.
    N Engl J Med. 2015 May 21;372(21):2018-28 PMID: 25891174
  8. Down-regulation of layilin, a novel hyaluronan receptor, via RNA interference, inhibits invasion and lymphatic metastasis of human lung A549 cells.
    Biotechnol Appl Biochem. 2008 Jun;50(Pt 2):89-96 PMID: 17822380
  9. The role of tumour-associated macrophages in bone metastasis.
    J Bone Oncol. 2016 Apr 08;5(3):135-138 PMID: 27761375
  10. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
    Gastroenterology. 2010 Mar;138(3):958-68 PMID: 19914252
  11. Molecular cloning and characterization of human chondrolectin, a novel type I transmembrane protein homologous to C-type lectins.
    Genomics. 2002 Jul;80(1):62-70 PMID: 12079284
  12. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.
    Nature. 2015 Jan 15;517(7534):386-90 PMID: 25363763
  13. Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles.
    J Cell Biol. 1998 Oct 19;143(2):429-42 PMID: 9786953
  14. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.
    Lancet Oncol. 2016 Jun;17(6):717-726 PMID: 27157491
  15. Japanese gastric cancer treatment guidelines 2014 (ver. 4).
    Gastric Cancer. 2017 Jan;20(1):1-19 PMID: 27342689
  16. Tumor-Associated Macrophages and Regulatory T Cells Infiltration and the Clinical Outcome in Colorectal Cancer.
    Arch Immunol Ther Exp (Warsz). 2017 Oct;65(5):445-454 PMID: 28343267
  17. Roles of layilin in TNF-α-induced epithelial-mesenchymal transformation of renal tubular epithelial cells.
    Biochem Biophys Res Commun. 2015 Nov 6;467(1):63-9 PMID: 26410531
  18. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
    N Engl J Med. 2015 Jun 25;372(26):2509-20 PMID: 26028255
  19. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy.
    Cancer Discov. 2014 May;4(5):522-6 PMID: 24795012
  20. Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.
    J Clin Oncol. 2010 Jul 20;28(21):3485-90 PMID: 20498386
  21. T-regulatory cells: key players in tumor immune escape and angiogenesis.
    Cancer Res. 2012 May 1;72(9):2162-71 PMID: 22549946
  22. Layilin, a novel integral membrane protein, is a hyaluronan receptor.
    Mol Biol Cell. 2001 Apr;12(4):891-900 PMID: 11294894
  23. Systematic pan-cancer analysis of tumour purity.
    Nat Commun. 2015 Dec 04;6:8971 PMID: 26634437
  24. Gene expression markers of Tumor Infiltrating Leukocytes.
    J Immunother Cancer. 2017 Feb 21;5:18 PMID: 28239471
  25. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles.
    Neoplasia. 2007 Feb;9(2):166-80 PMID: 17356713
  26. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.
    Immunity. 2016 Nov 15;45(5):1135-1147 PMID: 27851914
  27. Current status and future directions of the immune checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab in oncology.
    Ann Pharmacother. 2015 Aug;49(8):907-37 PMID: 25991832
  28. Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer.
    Clin Cancer Res. 2009 Dec 15;15(24):7642-7651 PMID: 19996206
  29. Depletion of plasmacytoid dendritic cells inhibits tumor growth and prevents bone metastasis of breast cancer cells.
    J Immunol. 2012 Nov 1;189(9):4258-65 PMID: 23018462
  30. Layilin is critical for mediating hyaluronan 35kDa-induced intestinal epithelial tight junction protein ZO-1 in vitro and in vivo.
    Matrix Biol. 2018 Mar;66:93-109 PMID: 28978412
  31. Immunotherapy in Gastrointestinal Cancers.
    Biomed Res Int. 2017;2017:4346576 PMID: 28758114
  32. Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis.
    Br J Cancer. 2014 Jul 29;111(3):559-67 PMID: 24937668
  33. Genome-wide association analysis identifies genetic correlates of immune infiltrates in solid tumors.
    PLoS One. 2017 Jul 27;12(7):e0179726 PMID: 28749946
  34. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.
    Lancet Oncol. 2017 Sep;18(9):1182-1191 PMID: 28734759
  35. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma.
    J Clin Oncol. 2012 Jul 20;30(21):2678-83 PMID: 22711850
  36. Tumor-infiltrating Neutrophils is Prognostic and Predictive for Postoperative Adjuvant Chemotherapy Benefit in Patients With Gastric Cancer.
    Ann Surg. 2018 Feb;267(2):311-318 PMID: 27763900
  37. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy.
    Genome Biol. 2016 Aug 22;17(1):174 PMID: 27549193
  38. Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing.
    Cell. 2017 Jun 15;169(7):1342-1356.e16 PMID: 28622514
  39. Secretion of inflammatory factors from chondrocytes by layilin signaling.
    Biochem Biophys Res Commun. 2014 Sep 12;452(1):85-90 PMID: 25150153
  40. Cancer Statistics, 2017.
    CA Cancer J Clin. 2017 Jan;67(1):7-30 PMID: 28055103
  41. Inferring tumour purity and stromal and immune cell admixture from expression data.
    Nat Commun. 2013;4:2612 PMID: 24113773
  42. Cancer microenvironment and inflammation: role of hyaluronan.
    Front Immunol. 2015 Apr 14;6:169 PMID: 25926834
  43. Hyaluronan and layilin mediate loss of airway epithelial barrier function induced by cigarette smoke by decreasing E-cadherin.
    J Biol Chem. 2012 Dec 7;287(50):42288-98 PMID: 23048036
Article Info
Journal
Frontiers in immunology
Abbr.
Front Immunol
ISSN
1664-3224
Published
2019-00-00
Epub
2019-00-29
Pages
6
Language
English
Region
Switzerland
NLM ID
101560960
PMCID
PMC6362421
Subset
IM
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