Actin-Associated Gene Expression is Associated with Early Regional Metastasis of Tongue Cancer
- 1 April 2021
- journal article
- research article
- Published by Wiley in The Laryngoscope
- Vol. 131 (4), 813-819
- https://doi.org/10.1002/lary.29025
Abstract
Objectives We aimed to analyze gene expression profile of tongue cancer associated with early lymph node metastasis using the cancer genome atlas (TCGA) data. Study design Basic research. Methods A total of 515 patients with matched RNAseq data of primary tumor and clinical data from TCGA data were extracted. To compare gene expression profile between early T-stage tongue cancer with cervical lymph node metastasis and late T-stage tongue cancer without cervical metastasis, genomic data of following two groups was assessed; 1) group 1: T1/2 and N2/3 (n = 41), 2) group 2: T4 and N0 (n = 65). Using R and limma package in bioconductor program, differentially expressed genes (DEGs) were extracted. Gene ontology and pathway enrichment analysis were performed using the DAVID online tool. FFPE tissue of 285 patients were evaluated for the validation of relevant genes by imunofluorescence (IF) and immunohistochemical (IHC) stain. Results A total of 225 DEGs were found, and 50 genes were highly significant with absolute fold change over eight. Gene ontology and pathway enrichment analysis revealed that most of the upregulated genes were associated with actin cytoskeleton and included following genes: ANKRD23, NO3, PDLIM3, MUSTN1, TNNT3, MYBPC1, MB, MYH3, TTN, ACTA1, and ACTC1. When comparing tongue cancer with cN0pN0 vs. pN0pN+ using the total tongue cancer cohort of TCGA, ACTA1 was the only parameter which was associated with hidden lymph node metastasis in T1/2 (P= .019). Perineural invasion was significantly associated with high expression of ACTA1 (P < .001). IF and IHC analysis revealed that actin was overexpressed, while E-cadherin and N-cadherin were not significantly different. Conclusions Actin associated genes, especially overexpression of ACTA1 may be associated with early regional metastasis of tongue cancer. Level of Evidence 3 Study design Basic researchLaryngoscope, 2020Keywords
Funding Information
- National Research Foundation of Korea (2018R1D1A1B07047534)
- Seoul National University Hospital
This publication has 26 references indexed in Scilit:
- Mesenchymal–epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancerCancer and Metastasis Reviews, 2012
- EPLIN downregulation promotes epithelial–mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasisOncogene, 2011
- A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neckOral Oncology, 2011
- Management of the clinically negative neck in early‐stage head and neck cancers after transoral resectionHead & Neck, 2010
- Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patientsHead & Neck Oncology, 2010
- The actin-binding and bundling protein, EPLIN, is required for cytokinesisCell Cycle, 2009
- Lamellipodia and filopodia in metastasis and invasionFEBS Letters, 2008
- Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongueOral Oncology, 2005
- Risk factors for late cervical lymph node metastases in patients with stage I or II carcinoma of the tongueHead & Neck, 2002
- Prognostic factors of clinically stage I and II oral tongue carcinoma—A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, martinez‐gimeno score, and pathologic featuresHead & Neck, 2002