For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
21
views
31
references
 Top references
cited by
146
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      214
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored.

          Methods

          We developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated.

          Results

          Computational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in both training and validation cohorts. These immune-hot patients exhibit significantly improved survival outcome and greater immune cell infiltration compared with immune-cold patients. Multivariate analysis revealed that the TILSig is an independent predictive factor after adjusting for other clinical factors. Further analysis accounting for TILSig and immune checkpoint gene revealed that the TILSig has a discriminatory power in patients with similar expression levels of immune checkpoint genes and significantly prolonged survival was observed for patients with low TILSig and low immune checkpoint gene expression implying a better response to immune checkpoint inhibitor (ICI) immunotherapy.

          Conclusions

          Our finding demonstrated the importance and value of lncRNAs in evaluating the immune infiltrate of the tumor and highlighted the potential of lncRNA coupled with specific immune checkpoint factors as predictive biomarkers of ICI response to enable a more precise selection of patients.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: found
          • Article: not found
          Is Open Access

          Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade.

          Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova … (2017)
          The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia.at/). Cellular characterization of the immune infiltrates showed that tumor genotypes determine immunophenotypes and tumor escape mechanisms. Using machine learning, we identified determinants of tumor immunogenicity and developed a scoring scheme for the quantification termed immunophenoscore. The immunophenoscore was a superior predictor of response to anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death protein 1 (anti-PD-1) antibodies in two independent validation cohorts. Our findings and this resource may help inform cancer immunotherapy and facilitate the development of precision immuno-oncology.
          Article 0 comments Cited 2104 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.

            Itai Yanai, Hila Benjamin, Michael Shmoish … (2005)
            Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression. To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62 839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index tau, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 50% of all expression patterns. We developed a binary classification, indicating for every gene the I(B) tissues in which it is overly expressed, and the 12-I(B) tissues in which it shows low expression. The 85 dominant midrange patterns with I(B)=2-11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny. All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803. doron.lancet@weizmann.ac.il Four tables available at the above site.
            Article 0 comments Cited 514 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas.

              Hirokazu Okayama, Takashi Kohno, Yuko Ishii … (2012)
              Activation of the EGFR, KRAS, and ALK oncogenes defines 3 different pathways of molecular pathogenesis in lung adenocarcinoma. However, many tumors lack activation of any pathway (triple-negative lung adenocarcinomas) posing a challenge for prognosis and treatment. Here, we report an extensive genome-wide expression profiling of 226 primary human stage I-II lung adenocarcinomas that elucidates molecular characteristics of tumors that harbor ALK mutations or that lack EGFR, KRAS, and ALK mutations, that is, triple-negative adenocarcinomas. One hundred and seventy-four genes were selected as being upregulated specifically in 79 lung adenocarcinomas without EGFR and KRAS mutations. Unsupervised clustering using a 174-gene signature, including ALK itself, classified these 2 groups of tumors into ALK-positive cases and 2 distinct groups of triple-negative cases (groups A and B). Notably, group A triple-negative cases had a worse prognosis for relapse and death, compared with cases with EGFR, KRAS, or ALK mutations or group B triple-negative cases. In ALK-positive tumors, 30 genes, including ALK and GRIN2A, were commonly overexpressed, whereas in group A triple-negative cases, 9 genes were commonly overexpressed, including a candidate diagnostic/therapeutic target DEPDC1, that were determined to be critical for predicting a worse prognosis. Our findings are important because they provide a molecular basis of ALK-positive lung adenocarcinomas and triple-negative lung adenocarcinomas and further stratify more or less aggressive subgroups of triple-negative lung ADC, possibly helping identify patients who may gain the most benefit from adjuvant chemotherapy after surgical resection. ©2011 AACR.
              Article 0 comments Cited 432 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Immunother Cancer
                Journal ID (iso-abbrev): J Immunother Cancer
                Journal ID (hwp): jitc
                Journal ID (publisher-id): jitc
                Title: Journal for Immunotherapy of Cancer
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2051-1426
                Publication date Collection: 2020
                Publication date (Electronic): 10 February 2020
                Volume: 8
                Issue: 1
                Electronic Location Identifier: e000110
                Affiliations
                [1 ] departmentSchool of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital , Wenzhou Medical University , Wenzhou, China
                [2 ] departmentDepartment of Orthopedic Surgery , Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing, China
                Author notes
                [Correspondence to ] Professor Meng Zhou, School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China; zhoumeng@ 123456wmu.edu.cn ; Professor Liangde Xu, School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China; xuld@ 123456eye.ac.cn
                Author information
                http://orcid.org/0000-0001-9987-9024
                Article
                Publisher ID: jitc-2019-000110
                DOI: 10.1136/jitc-2019-000110
                PMC ID: 7057423
                PubMed ID: 32041817
                SO-VID: 3e81d614-2e9b-4113-b1d3-253c749cbded
                Copyright © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
                License:

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date accepted : 28 December 2019
                Categories
                Subject: Immunotherapy Biomarkers
                Subject: 1506
                Subject: 2437
                Custom metadata
                special-feature unlocked

                Keywords: medicine,computational psychiatry,molecular immunogene,oncology
                Data availability:
                Keywords: medicine, computational psychiatry, molecular immunogene, oncology

                Comments

                Comment on this article

                scite_

                Similar content214

                See all similar

                Cited by159

                See all cited by

                Most referenced authors1,773

                See all reference authors