ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy globally. The etiology of HNSCC is multifactorial, including cellular stress induced by a tobacco smoking, tobacco chewing excess alcohol consumption, and human papillomavirus infection. The induction of stress includes autophagy as one of the response pathways in maintaining homeostatic equilibrium. We evaluated the expression of autophagy-related genes in HNSCC tissues from RNA sequencing datasets and identified 19 genes correlated with poor prognosis and 18 genes correlated with improved prognosis of HNSCC patients. Further analysis of independent gene expression datasets revealed that ATG12, HSP90AB1, and FKBP1A are overexpressed in HNSCC and correlate with poor prognosis, whereas the overexpression of ANXA1, FOS, and ULK3 correlates with improved prognosis. Using independent datasets, we also found that ATG12, HSP90AB1, and FKBP1A expression increased with an increase in the T-stage of HNSCC. Among all the datasets analyzed, FKBP1A was overexpressed in HNSCC and was strongly associated with lymph node metastasis in multiple in silico datasets. In conclusion, our analysis indicates dynamic alterations in autophagy genes during HNSCC and warrants further investigation, specifically on FKBP1A and its role in tumor progression and metastasis.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Lymphatic Metastasis , Prognosis , Squamous Cell Carcinoma of Head and Neck/genetics , Tacrolimus Binding Proteins/genetics , Up-RegulationABSTRACT
The current prevalence of diagnosable dementia in India is 1% of people over 60â¯years (~3.7 million people), but is estimated to increase significantly, as ~15% world's aged population (>65â¯years) would be resident here by 2020 (Shah et al., 2016). While several mutations that pose a familial risk have been identified, the ethnic background may influence disease susceptibility, clinical presentation and treatment response. In this study, we report a detailed characterization of two representative HiPSC lines from a well-characterized dementia cohort from India. Availability of these lines, and associated molecular and clinical information, would be useful in the detailed exploration of the genomic contribution(s) to AD.
