Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma |
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Authors: | QING GAO YUJING SHI YUANYUAN SUN SHU ZHOU ZEYUAN LIU XINCHEN SUN XIAOKE DI |
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Institution: | 1 Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China2 Department of Oncology, Jurong People’s Hospital, Jurong, 212499, China3 Department of Radiation Oncology, Nanjing Jiangning Hospital and the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211199, China |
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Abstract: | Aging is highly associated with tumor formation and progression. However, little research has explored the
association of aging-related lncRNAs (ARLs) with the prognosis and tumor immune microenvironment (TIME) of
head and neck squamous cell carcinoma (HNSCC). RNA sequences and clinicopathological data of HNSCC patients
and normal subjects were downloaded from The Cancer Genome Atlas. In the training group, we used Pearson
correlation, univariate Cox regression, least absolute shrinkage/selection operator regression analyses, and multivariate
Cox regression to build a prognostic model. In the test group, we evaluated the model. Multivariate Cox regression
was done to screen out independent prognostic factors, with which we constructed a nomogram. Afterward, we
demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent
receiver operating characteristics. Gene set enrichment analysis, immune correlation analysis, and half-maximal
inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to
predict immuno- and chemo-therapeutic responses. The most important LINC00861 in the model was examined in
HNE1, CNE1, and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2
using the LINC00861-pcDNA3.1 construct plasmid. In addition, CCK-8, Edu, and SA-β-gal staining assays were
conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells. The signature based on nine ARLs has
a good predictive value in survival time, immune infiltration, immune checkpoint expression, and sensitivity to
multiple drugs. LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells, and
LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal
carcinoma cell lines. This work built and verified a new prognostic model for HNSCC based on ARLs and mapped
the immune landscape in HNSCC. LINC00861 is a protective factor for the development of HNSCC. |
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Keywords: | Aging lncRNA HNSCC Prognosis Tumor immune microenvironment Bioinformatics |
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