國家衛生研究院 NHRI:Item 3990099045/13934
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 853775      Online Users : 1213
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13934


    Title: Identification of prognostic biomarkers originating from the tumor stroma of betel quid-associated oral cancer tissues
    Authors: Liu, YH;Chen, YL;Lai, TY;Ko, YC;Chou, YF;Chen, PR;Hsiao, JR;Chang, JY;Shiah, SG;Lee, JW;Yang, JL;Lin, SF
    Contributors: National Institute of Cancer Research;Institute of Biotechnology and Pharmaceutical Research
    Abstract: BackgroundPartial epithelial-mesenchymal transition (p-EMT) is a distinct clinicopathological feature prevalent in oral cavity tumors of The Cancer Genome Atlas. Located at the invasion front, p-EMT cells require additional support from the tumor stroma for collective cell migration, including track clearing, extracellular matrix remodeling and immune evasion. The pathological roles of otherwise nonmalignant cancer-associated fibroblasts (CAFs) in cancer progression are emerging. MethodsGene set enrichment analysis was used to reveal differentially enriched genes and molecular pathways in OC3 and TW2.6 xenograft tissues, representing mesenchymal and p-EMT tumors, respectively. R packages of genomic data science were executed for statistical evaluations and data visualization. Immunohistochemistry and Alcian blue staining were conducted to validate the bioinformatic results. Univariate and multivariate Cox proportional hazards models were performed to identify covariates significantly associated with overall survival in clinical datasets. Kaplan-Meier curves of estimated overall survival were compared for statistical difference using the log-rank test. ResultsCompared to mesenchymal OC3 cells, tumor stroma derived from p-EMT TW2.6 cells was significantly enriched in microvessel density, tumor-excluded macrophages, inflammatory CAFs, and extracellular hyaluronan deposition. By translating these results to clinical transcriptomic datasets of oral cancer specimens, including the Puram single-cell RNA-seq cohort comprising ~6000 cells, we identified the expression of stromal TGFBI and HYAL1 as independent poor and protective biomarkers, respectively, for 40 Taiwanese oral cancer tissues that were all derived from betel quid users. In The Cancer Genome Atlas, TGFBI was a poor marker not only for head and neck cancer but also for additional six cancer types and HYAL1 was a good indicator for four tumor cohorts, suggesting common stromal effects existing in different cancer types. ConclusionsAs the tumor stroma coevolves with cancer progression, the cellular origins of molecular markers identified from conventional whole tissue mRNA-based analyses should be cautiously interpreted. By incorporating disease-matched xenograft tissue and single-cell RNA-seq results, we suggested that TGFBI and HYAL1, primarily expressed by stromal CAFs and endothelial cells, respectively, could serve as robust prognostic biomarkers for oral cancer control.
    Date: 2021-11-16
    Relation: Frontiers in Oncology. 2021 Nov 16;11:Article number 769665.
    Link to: http://dx.doi.org/10.3389/fonc.2021.769665
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2234-943X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000726124800001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85120452176
    Appears in Collections:[Su-Fang Lin] Periodical Articles
    [Shine-Gwo Shiah] Periodical Articles
    [Jang-Yang Chang] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    ISI000726124800001.pdf6761KbAdobe PDF251View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback