Abstract：
Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the TTN mutant group showed shorter progression-free survival (p < 0.001) and overall survival (p < 0.001) than TTN wild-type group. Additionally, we discovered that the number of TTN mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (p < 0.05). And the number of TTN mutations per sample in POLE mutant group was greater than in the POLE wild-type group (p < 0.0001). In conclusion, TTN mutation may serve as a biomarker for EEC prognosis. TTN mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique.
摘要：
子宫内膜样子宫内膜癌（EEC）是发达地区普遍存在的妇科恶性肿瘤。然而,预测复发病例仍然具有挑战性，需要鉴定EEC复发的新型生物标志物。肿瘤突变负荷（TMB）的评估对于EEC患者的免疫治疗至关重要。然而,全外显子组测序(WES)和靶向测序都遇到了与应用相关的困难.鉴于此,TMB测量的标准化和简化技术势在必行。在这项研究中,我们对接受子宫切除术(CHCAMS队列)的25例EEC患者(12例复发病例和13例非复发病例)进行了WES治疗.我们还从TCGA网站获得了总共391个具有临床病理特征的肿瘤样本，以扩大研究队列。在CHCAMS队列中，与TTN野生型组相比,TTN突变组的无进展生存期(p<0.001)和总生存期(p<0.001)较短.此外,我们发现,在CHCAMS队列和TCGA队列中,每个样本的TTN突变数与TMB-WES显著相关(p<0.05).并且POLE突变体组中每个样品的TTN突变数量大于POLE野生型组(p<0.0001)。总之,TTN突变可作为EEC预后的生物标志物。TTN突变也与WES-TMB相关,并且可以是简化的TMB测量技术。
