Lu Hsueh-Ju, Su Chun-Wen, Su Shih-Chi, Chang Lun-Ching, Wu Ming-Fang, Lin Chiao-Wen, Yang Shun-Fa
Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Oral Dis. 2025 Mar;31(3):769-781. doi: 10.1111/odi.15124. Epub 2024 Sep 17.
Identifying the drive genes and inhibiting their significant signals were persistently the main concepts in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear.
A total of 120 OCSCC patients with corresponding pathologic specimens were collected in Taiwan. Whole-exome sequencing was done and the prognostic impact of each gene was analyzed. TCGA database was used to validate.
The incidences of caspase-8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase-8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) ([95% CI]: 3.83 [1.84-7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51 [1.00-2.29]). The 5-year OSs of the patients with or without caspase-8 mutation were 38.1% vs. 75.3% (p < 0.001) (HR [95% CI]: 3.264 [1.645-6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% (p = 0.048) (1.513 [1.001-2.288]) in the TCGA cohorts, respectively. Caspase-8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. CASP8 R127* and R494*, defined as pathogenic mutations in ClinVar, were presented in both cohorts.
Caspase-8 mutation was the most significant genetic alteration impacting prognosis.
识别驱动基因并抑制其重要信号一直是癌症治疗的主要理念。然而，对于口腔鳞状细胞癌（OCSCC），对总生存期（OS）最具影响的基因仍不清楚。
在台湾收集了120例伴有相应病理标本的OCSCC患者。进行了全外显子组测序，并分析了每个基因的预后影响。使用TCGA数据库进行验证。
台湾队列和TCGA队列中半胱天冬酶-8突变的发生率分别为22.1%和10.9%。在台湾队列中，半胱天冬酶-8突变是OS最显著的独立因素，调整后的风险比（HR）（[95%CI]：3.83[1.84 - 7.99]）。经TCGA数据库验证（HR[95%CI]：1.51[1.00 - 2.29]）。台湾队列中，有或无半胱天冬酶-8突变患者的5年总生存率分别为38.1%对75.3%（p < 0.001）（HR[95%CI]：3.264[1.645 - 6.438]），TCGA队列中分别为26.1%对49.0%（p = 0.048）（1.513[1.001 - 2.288]）。半胱天冬酶-8突变也分别与TNM I/II/III/IV期的不良预后单独相关。两个队列中均出现了ClinVar中定义为致病突变 的CASP8 R127和R494。
半胱天冬酶-8突变是影响预后最显著的基因改变。
