Integrating the genomic and TCR repertoire signatures predicts prognosis in primary epithelial ovarian cancer.

person Yang Xiang Peking Union Medical College Hospital, Beijing, China info_outline Yang Xiang, Shan Zhu, Dongyan Cao, Xi-Run Wan, Chunliu Zhang, Junjun Yang, Jiaxin Yang, Mei Yu, Ying Zhang, Tong Ren, Jing Wang, Peiling Li, Guo-Nan Zhang, Jing Bai, Yanfang Guan, Xuefeng Xia

Authors person Yang Xiang Peking Union Medical College Hospital, Beijing, China info_outline Yang Xiang, Shan Zhu, Dongyan Cao, Xi-Run Wan, Chunliu Zhang, Junjun Yang, Jiaxin Yang, Mei Yu, Ying Zhang, Tong Ren, Jing Wang, Peiling Li, Guo-Nan Zhang, Jing Bai, Yanfang Guan, Xuefeng Xia Organizations Peking Union Medical College Hospital, Beijing, China, Geneplus-Beijing Institute, Beijing, China, Hunan Cancer Hospital, Hunan, China, The Second Affiliated Hospital of Harbin Medical University, Harbin, China, Sichuan Cancer Hospital, Chengdu, China, Geneplus-Beijing, Beijing, China Abstract Disclosures Research Funding No funding received None Background: Epithelial ovarian cancer is one of the common causes of gynecologic cancer death around the world. Histologically, EOC is classified into 5 major sub-types: high-grade serous (HGSOC), low grade serous (LGSOC), clear cell (CCOC), endometrioid (ENOC) and mucinous (MOC). Baseline genomic and immunomicroenvironmental characteristics of treatment-naive patients may offer an insight into recurrent risks. Methods: 101 patients with treatment-naive EOC were enrolled, including 60 HGSOC, 14 LGSOC, 8 ENOC, 14 CCOC, 5 MOC. Tumor tissues and paired peripheral blood samples were collected and performed with target sequencing of 1021 genes and TCR repertoire sequencing. Patients were intensively followed up for at least one year. To explored the molecular characteristic among 5 sub-types, genomic features and TCR repertoire signature were evaluated. Results: The mutation rate of PTEN loss was comparable among 5 sub-types for 53.3% (32/60) in HGSOC, 57.1% (8/14) in LGSOC, 42.9% (6/14) in CCOC, 50% (4/8) in ENOC, 40% (2/5) in MOC. Patients with PTEN loss tended to have lower tumor mutation burden (p = 0.077, Wilcoxon test), especially in HGSOC (p = 0.048, Wilcoxon test). Patients with CCOC and ENOC had significantly higher clonality, which indicates T cell expansion, than SOC tumor (HGSOC, LGSOC) (p = 0.036, Wilcoxon test). Moreover, the proportion of top 10, top 50 and top 100 T cell clones were all significantly higher in CCOC and ENOC than that in SOC(p = 0.0072, 0.0041, 0.0058, Wilcoxon test).In addition, richness and Shannon-index, two metrics for T cell diversity, were significantly higher in SOC comparing with CCOC and ENOC(p = 0.032, 0.0018, Wilcoxon test). After integrated the genomic and TCR features, more favorite disease-free survival (DFS) was found in patients with PTEN loss wild type, higher TMB, higher clonality and lower Shannon-index (p = 0.041, HR = 0.24, Mantel–Cox test). Conclusions: Our results highlight the traits of genomic and TCR repertoire in different subtypes of epithelial ovarian cancer and their prognostic significance. Interestingly, higher T cell clonality in CCOC and ENOC patients were found, which suggested the anti-cancer immune response was better activated. However, our study gets a preliminary result, and further verification work is needed.