Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Oral Oncol. 2020 Jun;105:104657. doi: 10.1016/j.oraloncology.2020.104657. Epub 2020 Mar 31.
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.
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.
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.
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.
RSPO（R-Spondins）和富含亮氨酸重复的 G 蛋白偶联受体（LGRs）通过增强 WNT/β-catenin 信号通路在胚胎和癌症发育中发挥关键作用，但它们在头颈部鳞状细胞癌（HNSCC）中的预后意义尚不清楚。HNSCC 是一组肿瘤，包括口咽鳞状细胞癌（OPSCC）等，其中一些是由人乳头瘤病毒（HPV）引起的。我们旨在研究 RSPO2 和 LGR4/5/6 对 HNSCC 患者总生存（OS）和无病生存（DFS）的潜在预后价值。
我们通过免疫组织化学检测了 126 例 HNSCC 患者的 RSPO 和 LGR 表达。此外，为了外部验证我们的发现，我们使用独立的二级数据集检测了 RSPO2 和 LGR6 mRNA 表达水平。
我们队列的五年 OS 为 59.6%。在多变量分析中，RSPO2 和 LGR4/5/6 表达与 OS 或 DFS 无关。然而，在 HPV+病例（n=26，33%）中，我们观察到 RSPO2 表达（五年 OS：RSPO+45.4% vs. RSPO2-84.6%）和 LGR6 表达（五年 OS：LGR6+52.9% vs. LGR6-100%）与 OS 相关。发现 HPV 状态与 RSPO2 和 LGR6 之间存在交互作用。与 HPV+/LGR6-患者相比，HPV+/LGR6+患者死亡的可能性增加了 12 倍。这些结果在第二个数据集中得到了复制。
我们的结果表明，LGR6 的表达状态对 HPV+OPSCC 的侵袭性有影响，这可能使其成为识别死亡风险高的患者的有用标志物。
