Identification of new candidate therapeutic target genes in head and neck squamous cell carcinomas

Abstract

BackgroundWe aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance.MethodsWe retrieved 96 HNSCC patients who underwent primary surgery. Real-time quantitative RT-PCR was used to analyze a panel of 42 genes coding for major druggable proteins. Univariate and multivariate analyses were performed to assess the prognostic significance of overexpressed genes.ResultsMedian age was 56 years [35–78]. Most of patients were men (80%) with a history of alcohol (70.4%) and/or tobacco consumption (72.5%). Twelve patients (12%) were HPV-positive. Most significantly overexpressed genes involved cell cycle regulation (CCND1 [27%], CDK6 [21%]), tyrosine kinase receptors (MET [18%], EGFR [14%]), angiogenesis (PGF [301%], VEGFA [14%]), and immune system (PDL1/CD274 [28%]). PIK3CA expression was an independent prognostic marker, associated with shorter disease-free survival.ConclusionsWe identified druggable overexpressed genes associated with a poor outcome that might be of interest for personalizing treatment of HNSCC patients.

Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

“…PD-L1 was the most studied biomarker, analyzed in 53 studies [10,11,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][34][35][36][37][39][40][41][42][43][44][45][46]48,50,54,[59][60][61]64,65,67,68,[70][71][72][74][75][76][77][78]80,81,86]...…”

“…Moreover, fractionated chemoradiation leads to quantifiable effects and balance between suppressive and stimulatory mechanisms, which will be helpful when combined with immune checkpoint blockade [59]. Many genes are involved in tumorigenesis pathways, but of interest, six genes (PGF, PD-L1/CD274, CDK6, EGFR, MET, VEGFA) are overexpressed in HNSCC and associated with poorer outcome [39]. Furthermore, mPDCD1 (methylated PD-1 promotor) might potentially serve as a predictive biomarker for the response to immunotherapies targeting the PD-1/PD-L1 axis [66].…”

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

“…There have been implications for differences in response rates between HPV-negative and HPVassociated head and neck cancers; however, these indicators have not yet led to a change in therapy guidelines (14)(15)(16)(17). Recent ground-breaking studies have identified a large variety of inter-individual and intra-individual heterogeneity as a key reason for treatment resistance (18)(19)(20)(21). Several cancer cell clones with unique sets of driver mutations can be found within a single tumor (22).…”

Identification of miRNA-mRNA crosstalk in laryngeal squamous cell carcinoma

“…The VEGF family serves key roles in tumor angiogenesis. It is reported that PGF is over expressed in head and neck squamous cell carcinoma, which is involved in angiogenesis (28). PGF is upregulated in breast cancer and the increased expression of PGF is associated with recurrence, metastasis and poor prognosis in patients with breast cancer (29).…”