Mutations inKeap1/Nrf2in head and neck cancer result in abnormal cell growth. Progenitor cells, bulk tumor cells, and head and neck cancer stem cells (HN-CSCs) may all harbor these mutations. Nevertheless, whetherKeap1/Nrf2mutations in HN-CSCs have an impact on clinical outcomes is unknown. Cancerous HN-CSCs and benign stem cells were obtained from freshly resected head and neck cancer patients (n = 50) via flow cytometry cell sorting and tested forKeap1/Nrf2mutations. The existence ofKeap1/Nrf2mutations in HN-CSCs, as well as their correlations with tumor mutations, pathologic tumor stage, tumor histologic grades, lung metastasis, treatment outcomes, and the patient’s age and conditions, are assessed at the last follow-up visit. Thirteen tumors were found to haveKeap1/Nrf2mutations in their HN-CSCs. More than half of the lung metastases and disease progression occurred in HN-CSCs with mutations. Patients whose tumors carriedKeap1/Nrf2mutations in their HN-CSCs had significantly shorter progression-free survival, overall survival, and time of treatment failure than their non-HN-CSC counterparts. These associations were partly driven by HN-CSCs, in whichKeap1/Nrf2mutations were overrepresented in fast progressors and associated with an increased risk of disease progression. Our findings suggest that molecular genotyping of HN-CSCs may facilitate personalized treatment strategies and assist in identifying patients who are likely to benefit from chemotherapy.
头颈部癌症中的Keap1/Nrf2基因突变可导致细胞异常增殖。祖细胞、肿瘤主体细胞及头颈癌干细胞均可能携带此类突变。然而，头颈癌干细胞中的Keap1/Nrf2突变是否影响临床预后尚不明确。本研究通过流式细胞分选技术从新鲜切除的头颈癌组织样本（n=50）中分离恶性头颈癌干细胞与良性干细胞，并检测其Keap1/Nrf2突变状态。在末次随访时评估头颈癌干细胞中Keap1/Nrf2突变的存在情况，及其与肿瘤突变负荷、病理分期、组织学分级、肺转移、治疗结局、患者年龄和健康状况的关联性。结果显示，13例肿瘤的头颈癌干细胞存在Keap1/Nrf2突变。超过半数的肺转移和疾病进展事件发生在携带此类突变的头颈癌干细胞群体中。与头颈癌干细胞未突变组相比，头颈癌干细胞携带Keap1/Nrf2突变患者的无进展生存期、总生存期及治疗失败时间均显著缩短。这种关联部分由头颈癌干细胞驱动，其Keap1/Nrf2突变在快速进展者中过度表达，并与疾病进展风险升高相关。本研究提示，头颈癌干细胞的分子基因分型可能有助于制定个体化治疗策略，并协助识别可能从化疗中获益的患者群体。
肿瘤(癌症)患者之家