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C10orf55, CASC2, and SFTA1P lncRNAs Are Potential Biomarkers to Assess Radiation Therapy Response in Head and Neck
Anna Paszkowska1,2,3, Tomasz Kolenda1,3, Kacper Guglas1,3,4
1Laboratory of Cancer Genetics, Greater Poland Cancer Center, Garbary Street 15, 61-866 Poznan, Poland.
Abstract:
Long non-coding RNAs have proven to be important molecules in carcinogenesis. Due to little knowledge about them, the molecular mechanisms of tumorigenesis are still being explored. The aim of this work was to study the effect of ionizing radiation on the expression of lncRNAs in head and neck squamous cell carcinoma (HNSCC) in patients responding and non-responding to radiotherapy. The experimental model was created using a group of patients with response (RG, n = 75) and no response (NRG, n = 75) to radiotherapy based on the cancer genome atlas (TCGA) data. Using the in silico model, statistically significant lncRNAs were defined and further validated on six HNSCC cell lines irradiated at three different doses. Based on the TCGA model, C10orf55, C3orf35, C5orf38, CASC2, MEG3, MYCNOS, SFTA1P, SNHG3, and TMEM105, with the altered expression between the RG and NRG were observed. Analysis of pathways and immune profile indicated that these lncRNAs were associated with changes in processes, such as epithelial-to-mesenchymal transition, regulation of spindle division, and the p53 pathway, and differences in immune cells score and lymphocyte infiltration signature score. However, only C10orf55, CASC2, and SFTA1P presented statistically altered expression after irradiation in the in vitro model. In conclusion, the expression of lncRNAs is affected by ionization radiation in HNSCC, and these lncRNAs are associated with pathways, which are important for radiation response and immune response. Potentially presented lncRNAs could be used as biomarkers for personalized radiotherapy in the future. However, these results need to be verified based on an in vitro experimental model to show a direct net of interactions.
Insights
Ionizing radiation alters long non-coding RNA (lncRNA) expression in head and neck squamous cell carcinoma (HNSCC), impacting radiation response and immune profiles. Specific lncRNAs may serve as future biomarkers for personalized radiotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Long non-coding RNAs (lncRNAs) play a role in cancer development, but their specific functions in head and neck squamous cell carcinoma (HNSCC) tumorigenesis remain underexplored.
- Understanding how ionizing radiation affects lncRNA expression is crucial for elucidating treatment response mechanisms in HNSCC.
Purpose of the Study:
- To investigate the impact of ionizing radiation on lncRNA expression in HNSCC patients with varying responses to radiotherapy.
- To identify specific lncRNAs associated with radiotherapy response and explore their potential roles in molecular pathways and immune responses.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) data to establish an in silico model comparing lncRNA expression in radiotherapy responders (RG) and non-responders (NRG).
- Validated significant lncRNAs in vitro using six HNSCC cell lines exposed to three different doses of ionizing radiation.
- Analyzed associated pathways, immune profiles, and cellular processes linked to differentially expressed lncRNAs.
Main Results:
- An in silico model identified nine lncRNAs (C10orf55, C3orf35, C5orf38, CASC2, MEG3, MYCNOS, SFTA1P, SNHG3, TMEM105) with altered expression between RG and NRG groups.
- These lncRNAs were linked to epithelial-to-mesenchymal transition, spindle division regulation, p53 pathway, and immune cell/lymphocyte infiltration scores.
- In vitro validation confirmed altered expression for C10orf55, CASC2, and SFTA1P post-irradiation.
Conclusions:
- Ionizing radiation significantly affects lncRNA expression in HNSCC.
- The identified lncRNAs are associated with critical pathways influencing radiation and immune responses.
- Specific lncRNAs, such as C10orf55, CASC2, and SFTA1P, show potential as biomarkers for predicting radiotherapy outcomes and enabling personalized treatment strategies in HNSCC.
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