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Cancer Cell International

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Open Access 01-12-2022 | Primary research

Immune-related lncRNA classification of head and neck squamous cell carcinoma

Authors: Ruoyan Cao, Lin Cui, Jiayu Zhang, Xianyue Ren, Bin Cheng, Juan Xia

Published in: Cancer Cell International | Issue 1/2022

Abstract

Background

Long noncoding RNAs (lncRNAs) play a critical role in innate and adaptive immune responses. Thus, we aimed to identify ideal subtypes for head and neck squamous cell carcinoma (HNSCC) based on immune-related lncRNAs.

Methods

TCGA HNSCC cohort was divided into two datasets (training and validation dataset), and 960 previously characterized immune-related lncRNAs were extracted for non-negative matrix factorization analysis. We characterized our HNSCC subtypes based on biological behaviors, immune landscape and response to immunotherapy in both training and validation cohort. A lncRNA-signature was generated to predict our HNSCC subtypes, and essential lncRNAs involved in tumor microenvironment (TME) were identified.

Results

We developed and validated two HNSCC subtypes (C1 and C2) based on the 70 lncRNAs in the training and validation cohort. C2 subtype displayed good prognosis, high immune cell infiltration, immune-related genes expression and sensitivity to PD-1 blockade. C1 subtype was associated with high activity of mTORC1 signaling and glycolysis as well as high fraction of inactive immune cells. Finally, we generated a 31-lncRNA signature that could predict our above subtypes with high accurate. Additionally, TRG-AS1 was identified as the essential lncRNA involving TME formation. Knockdown of TRG-AS1 inhibited the expression of HLA-A, HLA-B, HLA-C, CXCL9, CXCL10 and CXCL11. High expression of TRG-AS1 indicated a favorable prognosis in HNSCC and anti-PD-L1 cohort (IMvigor210).

Conclusions

Our study establishes a novel HNSCC classification on the basis of 31-lncRNA, helping to identify beneficiaries for anti-PD-1 treatment. In addition, a critical lncRNA TRG-AS1 is identified as a new potential prognosis biomarker as well as therapeutic target.

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Title: Immune-related lncRNA classification of head and neck squamous cell carcinoma
Authors: Ruoyan Cao
Lin Cui
Jiayu Zhang
Xianyue Ren
Bin Cheng
Juan Xia
Publication date: 01-12-2022
Publisher: BioMed Central
Published in: Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-022-02450-z

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