FN1 promotes prognosis and radioresistance in head and neck squamous cell carcinoma: From radioresistant HNSCC cell line to integrated bioinformatics methods

Abstract

Background: Radioresistance in head and neck squamous cell carcinoma (HNSCC) patients means response failure to current treatment. In order to screen radioresistant biomarkers and mechanisms associated with HNSCC, differentially expressed genes (DEGs) associated with radioresistance in HNSCC were investigated.Methods: The HNSCC cell line with radioresistance, Hep2-R, was established and detected the radiosensitivity using MTT, colony formation assay and flow cytometry analysis. Clariom™ D chip was applied to compare DEGs between Hep2 and Hep2-R groups and build the differential gene expression profiles associated with radioresistance in HNSCC. Bioinformatic analysis were used to find biological functions and pathways that related to radioresistance in HNSCC, including cell adhesion, cytochrome P450 and drug metabolism. Gene Expression Omnibus (GEO) datasets were selected to verify DEGs between HNSCC radioresistant cells and tissues. The representation of DEGs were validated between HNSCC patients with complete response and post-operative radiation therapy failure. In addition, we evaluated the clinical prognosis of DEGs using The Cancer Genome Atlas (TCGA) database.Results: 2,360 DEGs (|Fold Change|>1.5, p < 0.05) were identified between Hep2 and Hep2-R, including 1,144 upregulated DEGs and 1,216 downregulated DEGs. They were further verified by HNSCC radioresistant cells and tissues in GEO. 13 radioresistant DEGs showed same difference in expression level between cells and tissues. By comparing 13 DEGs with HNSCC patients, upregulations of FN1, SOX4 and ETV5 were found identical with above results. Only FN1 was a prognostic indicator of HNSCC in TCGA.Conclusion: FN1 is the potential novel biomarker for predicting poor prognosis and radioresistance in HNSCC patients. Overexpression of FN1 plays an important role in the tumorigenesis, prognosis and radioresistance of HNSCC.

Prognostic Biomarkers after Radiotherapy for Nonsmall Cell Lung Cancer Based on Bioinformatics Analysis

“…Studies on FN1 and radioresistance have focused on patients treated with radiotherapy for head and neck tumors. And among patients with HNSCC (head and neck squamous cell carcinoma) in complete remission and those who failed postoperative radiotherapy, FN1 overexpression plays an important role in the development, prognosis, and radioresistance of HNSCC and is a potential new biomarker for predicting poor prognosis and radioresistance in patients with head and neck squamous cell carcinoma [ 14 ]. This study found that FN1 could be used as a potential biomarker for the efficacy and prognosis of radiotherapy in NSCLC.…”