4.7 Article

Long non-coding RNA C5orf64 is a potential indicator for tumor microenvironment and mutation pattern remodeling in lung adenocarcinoma

Journal

GENOMICS
Volume 113, Issue 1, Pages 291-304

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2020.12.010

Keywords

LncRNA; C5orf64; LUAD; TME; TMB; Prognosis

Funding

  1. National Natural Science Foundation of China [81672288]
  2. Shandong Province Key RD Plan [2018GSF118028]
  3. Natural Science Foundation of Shandong Province [ZR2019PH002]
  4. Shandong Provincial Hospital Research Incubation Fund

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This study explored the synergistic and antagonistic effects of tumor microenvironment and tumor mutation pattern on lung adenocarcinoma. A 14-lncRNA immune-related signature, with C5orf64 identified as a potential indicator for TME modulation and tumor mutation pattern remodeling, was developed through analysis of immune-related genes and construction of a ceRNA network. High expression of PD-1, PD-L1 and CTLA-4 was demonstrated in high-level C5orf64 groups, while a negative correlation was observed between C5orf64 and TP53 mutation frequency. A novel model based on age, tumor stage and immune-related lncRNA signature was proposed.
Understanding the synergistic and antagonistic effects of tumor microenvironment (TME) and tumor mutation pattern on lung adenocarcinoma (LUAD) is urgently needed. Herein, we applied ESTIMATE and CIBERSORT methods to calculate the ratio of immune and stromal components and TIICs proportion of LUAD samples from TCGA database. Immune-related genes were analyzed by Lasso regression analysis and used for ceRNA network construction. A 14-lncRNA immune-related signature was developed, among which C5orf64 was found to be positively correlated with abundances of M2 macrophages, monocytes, eosinophils and neutrophils, but negatively correlated with Tregs and plasma cells. PD-1, PD-L1 and CTLA-4 were demonstrated to be high expressed in high-level C5orf64 groups. However, C5orf64 had a negative correlation with TP53 mutation frequency. A novel model was built based on age, tumor stage and immune-related lncRNA signature. To conclude, lncRNA C5orf64 had potential to be an indicator for TME modulation and tumor mutation pattern remodeling in LUAD.

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