Epithelial stem cell marker LGR6 expression identifies a low-risk subgroup in human papillomavirus positive oropharyngeal squamous cell carcinoma.
OBJECTIVES
R-Spondins (RSPOs) and leucine-rich repeat-containing G-protein coupled receptors (LGRs) play a critical role in embryonic and cancer development through potentiation of WNT/ß-catenin signaling, but their prognostic significance in head and neck squamous cell carcinoma (HNSCC) is still unclear. HNSCC is a group of neoplasms that include, amongst others, oropharyngeal squamous cell carcinoma (OPSCC), some of which are induced by human papillomavirus (HPV). We aimed to investigate the potential prognostic value of RSPO2 and LGR4/5/6 on overall survival (OS) and disease-free survival (DFS) in HNSCC patients.


METHODS
We examined RSPO and LGR expression by means of immunohistochemistry in 126 HNSCC patients. Furthermore, in order to validate our findings externally, we examined RSPO2 and LGR6 mRNA expression levels using independent secondary datasets.


RESULTS
The five-year OS of our cohort was 59.6%. RSPO2 and LGR4/5/6 expression were not associated with OS or DFS in multivariable analyses. Within the HPV+ cases (n = 26, 33%), however, we observed a difference in OS by RSPO2 expression (5-year OS: RSPO+ 45.4% vs. RSPO2- 84.6%) and LGR6 expression (5-year OS: LGR6+ 52.9% vs. LGR6-100%). Evidence for an interaction of HPV status with RSPO2 and LGR6 was found for OS. Relative to HPV+/LGR6- patients, HPV+/LGR6+ patients were 12 times more likely to die. These results were replicated in the second dataset.


CONCLUSION
Our results indicated that the expression status of LGR6 had an influence on the aggressiveness of HPV+ OPSCC, potentially making this receptor a useful marker for identifying patients with a high risk of death.
['Jank|Bernhard J|BJ|', 'Kadletz|Lorenz|L|', 'Dunkler|Daniela|D|', 'Haas|Markus|M|', 'Schnoell|Julia|J|', 'Kenner|Lukas|L|', 'Heiduschka|Gregor|G|']
D000368:Aged D015331:Cohort Studies D018572:Disease-Free Survival D005260:Female D006801:Humans D007150:Immunohistochemistry D008297:Male D008875:Middle Aged D009959:Oropharyngeal Neoplasms D027383:Papillomaviridae D030361:Papillomavirus Infections D057285:Precision Medicine D043562:Receptors, G-Protein-Coupled D012189:Retrospective Studies
Stem cell marker Human papillomavirus Head and neck squamous cell carcinoma Survival Precision medicine