TTN Mutation in Endometrial Endometrioid Carcinoma Is Associated with Poor Clinical Outcomes and High Tumor Mutation Burden

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.

Keywords:

• Endometrial endometrioid carcinoma
• whole-exome sequencing
• TTN
• POLE

Ethics statement

The studies involving human participants were reviewed and approved by the Institutional Review Board of Cancer Hospital, Chinese Academy of Medical Sciences (IRB number: 20/410: 2606) and obtained written consent from all patients.

Author contributions

Pinli Yue, Lihong Li, Jiarun Zhu, and Luyuan Li contributed equally to this work. Guangwen Yuan and Yan Song conceived the study. Pinli Yue and Lihong Li carried out experiments. Lihong Li, Pinli Yue, and Jiarun Zhu were involved in analyzing the data. Pinli Yue, Lihong Li, and Luyuan Li were involved in interpreting the data. Lihong Li and Pinli Yue wrote the paper. Guangwen Yuan and Yan Song are co-corresponding authors.

Disclosure statement

The authors declare no competing interests.

Data availability statement

Any additional data (beyond those included in the main text and Supplementary Information) that support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This work was supported by the Beijing Hope Run Special Fund of the Cancer Foundation of China [Grant Nos. LC2020A08 and LC2020B21] and Special Research Fund for Central Universities, Peking Union Medical College [Grant No. 3332023032].