| Summary: | Jincheng Ma,1– 3,* Jiansong Lin,4,* Xite Lin,1– 3 Yuan Ren,1– 3 Dabin Liu,5 Shuting Tang,1– 3 Leyi Huang,1– 3 Shuxia Xu,4 Xiaodan Mao,1– 3 Pengming Sun1– 3,5 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian Province, People’s Republic of China; 4Department of Pathology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Gynecology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodan Mao; PengMing Sun, Email maodan1985@fjmu.edu.cn; sunfemy@hotmail.comObjective: This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation.Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann–Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC.Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d.Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.Keywords: endometrial cancer, mismatch repair-deficiency, immune, molecular classification, MutL, MutS
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