Abstract 443P
Background
Head-Neck Squamous Cell Carcinoma (HNSCC) is the sixth most prevalent neoplasm induced due to a wide range of genetic and epigenetic alterations. Large Tumor Suppressor gene (LATS1) is a tumor suppressor gene that suppresses tumor development by regulating cell proliferation and apoptosis.
Methods
We analyzed the expression, promoter methylation, and mutation status of LATS1 gene from publicly available HNSCC-TCGA (n=523) dataset using cBioPortal, and MEXPRESS web servers. GEPIA2 was utilized to filter out the positively and negatively correlated genes with LATS1. Gene Set Enrichment Analysis (GSEA), DAVID, and STRING were used for functional and PPI enrichment analysis. To validate the methylation status of LATS1 gene in our population, blood samples from 50 HNSCC patients and 20 healthy individuals were collected. DNA was extracted and the methylation status of LATS1 gene was studied by performing methylation-specific polymerase chain reaction (MS-PCR).
Results
Higher expression and lower methylation of LATS1 gene were observed in HNSC cases as compared with normal samples (p < 0.05). Our data revealed that 19 out of 50 patients (38.0%) were found to be methylated for LATS1 gene in OSCC patients. In mutation analysis, LATS1 gene was mutated in 29 cases out of 523 cases approximately 6% of which H227Q, R767L, and P375S missense mutations were commonly seen. RBM16, SHPRH, and TAOK1 genes positively correlate while TIAF1, USMG5, and ATPIF1 genes were negatively correlated genes with LATS1 expression in HNSC. On Gene Ontology (GO) analysis these PPI genes were enriched in cell differentiation regulation, hemopoiesis, and Hippo signaling pathway. Moreover, higher expression and lower methylation levels of LATS1 gene were found to be statistically significantly associated with patients consuming alcohol, chewing tobacco, and having a smoking history frequently (p-value < 0.005). Poor overall survival was observed in HNSC patients having higher LATS1 expression as compared with patients having lower LATS1 gene expression (P= 0.21).
Conclusions
LATS1 hypermethylation plays a significant role in the diagnosis of HNSC patients with poor diagnosis and may be a useful as a diagnostic biomarker.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.