ArticleFrontiers in oncology2021
Molecular Interplays Between Cell Invasion and Radioresistance That Lead to Poor Prognosis in Head-Neck Cancer.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 15 citations in OpenAlex.
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- The significance of CD49f expression in pediatric B-cell acute lymphoblastic leukemia.American journal of clinical pathology · 2025Article
- Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma.Clinical and experimental otorhinolaryngology · 2025Article
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- Uptake of H-ferritin by Glioblastoma stem cells and its impact on their invasion capacity.Journal of cancer research and clinical oncology · 2023Article
- Integrated bioinformatics analysis of differentially expressed genes in the temporomandibular joint internal derangement.Clinical and experimental dental research · 2023Article
- Overexpression of CD73 is associated with recurrence and poor prognosis of gingivobuccal oral cancer as revealed by transcriptome and deep immune profiling of paired tumor and margin tissues.Cancer medicine · 2023Article
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- Targeted Profiling of Epitranscriptomic Reader, Writer, and Eraser Proteins Accompanied with Radioresistance in Breast Cancer Cells.Analytical chemistry · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer metastasis and recurrence after radiotherapy are the significant causes of poor prognosis in head-neck cancer (HNC). Clinically, it is commonly found that patients with either condition may accompany the outcome of the other. We hypothesized that HNC cells might exhibit a cross-phenotypic attribute between cell invasion and radioresistance. To discover effective biomarkers for the intervention of aggressive cancer at one time, the potential molecules that interplay between these two phenotypes were investigated. MATERIALS AND
methodsThree isogenic HNC cell sublines with high invasion or radioresistance properties were established. Transcriptomic and bioinformatic methods were used to globally assess the phenotypic-specific genes, functional pathways, and co-regulatory hub molecules. The associations of gene expressions with patient survival were analyzed by Kaplan-Meier plotter, a web-based tool, using the HNSCC dataset (n=500). The molecular and cellular techniques, including RT-qPCR, flow cytometry, cell invasion assay, and clonogenic survival assay, were applied.
resultsThe phenotypic crosstalk between cell invasion and radioresistance was validated, as shown by the existence of mutual properties in each HNC subline. A total of 695 genes was identified in associations with these two phenotypes, including 349 upregulated and 346 downregulated in HNC cells. The focal adhesion mechanism showed the most significant pathway to co-regulate these functions. In the analysis of 20 up-regulatory genes, a general portrait of correlative expression was found between these phenotypic cells (r=0.513, p=0.021), and nine molecules exhibited significant associations with poor prognosis in HNC patients (HR>1, p<0.050). Three hub genes were identified (ITGA6, TGFB1, and NDRG1) that represented a signature of interplayed molecules contributing to cell invasion, radioresistance and leading to poor prognosis. The ITGA6 was demonstrated as a prominent biomarker. The expression of ITGA6 correlated with the levels of several extracellular and apoptotic/anti-apoptotic molecules. Functionally, silencing ITGA6 suppressed cell migration, invasion, and attenuated radioresistance in HNC cells.
conclusionsA panel of interplay molecules was identified that contribute to cell invasion and radioresistance, leading to poor prognosis. These panel molecules, such as ITGA6, may serve as predictive markers of radioresistance, prognostic markers of metastasis, and molecular therapeutic targets for refractory HNC.
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