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      Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape

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          Abstract

          Introduction:

          Molecular subtyping of lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) reveal biologically diverse tumors that vary in their genomic and clinical attributes.

          Methods:

          Published immune cell signatures and several lung AD and SCC gene expression data sets, including The Cancer Genome Atlas, were used to examine immune response in relation to AD and SCC expression subtypes. Expression of immune cell populations and other immune related genes, including CD274 molecule gene ( CD274) (programmed death ligand 1), was investigated in the tumor microenvironment relative to the expression subtypes of the AD (terminal respiratory unit, proximal proliferative, and proximal inflammatory) and SCC (primitive, classical, secretory, and basal) subtypes.

          Results:

          Lung AD and SCC expression subtypes demonstrated significant differences in tumor immune landscape. The proximal proliferative subtype of AD demonstrated low immune cell expression among ADs whereas the secretory subtype showed elevated immune cell expression among SCCs. Tumor expression subtype was a better predictor of immune cell expression than CD274 (programmed death ligand 1) in SCC tumors but was a comparable predictor in AD tumors. Nonsilent mutation burden was not correlated with immune cell expression across subtypes; however, major histocompatibility complex class II gene expression was highly correlated with immune cell expression. Increased immune and major histocompatibility complex II gene expression was associated with improved survival in the terminal respiratory unit and proximal inflammatory subtypes of AD and in the primitive subtype of SCC.

          Conclusions:

          Molecular expression subtypes of lung AD and SCC demonstrate key and reproducible differences in immune host response. Evaluation of tumor expression subtypes as potential biomarkers for immunotherapy should be investigated.

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          Author and article information

          Journal
          101274235
          33311
          J Thorac Oncol
          J Thorac Oncol
          Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
          1556-0864
          1556-1380
          7 May 2019
          21 March 2017
          June 2017
          10 June 2019
          : 12
          : 6
          : 943-953
          Affiliations
          [a ]GeneCentric Diagnostics, Durham, North Carolina
          [b ]Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
          [c ]Department of Genetics, University of North Carolina, Chapel Hill, North Carolina
          Author notes
          [* ]Address for correspondence: Hawazin Faruki, DrPH, GeneCentric Diagnostics, 280 South Mangum St., Suite 350, Durham, NC 27701. Hawazin@ 123456genecentric.com
          Article
          PMC6557266 PMC6557266 6557266 nihpa1011979
          10.1016/j.jtho.2017.03.010
          6557266
          28341226
          c1031c8a-a220-4606-a0f9-3d8893c05ae5
          History
          Categories
          Article

          PD-L1,Gene expression,Squamous cell carcinoma,Lung cancer,Adenocarcinoma,Immune response

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