Identification of clinical and molecular features of recurrent serous borderline ovarian tumour

Ziyang Lu; Fanghe Lin; Tao Li; Jinhui Wang; Cenxi Liu; Guangxing Lu; Bin Li; MingPei Pan; Shaohua Fan; Junqiu Yue; He Huang; Jia Song; Chao Gu; Jin Li

doi:10.1016/j.eclinm.2022.101377

Identification of clinical and molecular features of recurrent serous borderline ovarian tumour

EClinicalMedicine. 2022 Apr 8:46:101377. doi: 10.1016/j.eclinm.2022.101377. eCollection 2022 Apr.

Authors

Ziyang Lu¹, Fanghe Lin², Tao Li³, Jinhui Wang¹, Cenxi Liu¹, Guangxing Lu¹, Bin Li¹, MingPei Pan¹, Shaohua Fan¹, Junqiu Yue⁴, He Huang¹, Jia Song⁵, Chao Gu¹, Jin Li^{1

6}

Affiliations

¹ State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Institute of Metabolism and Integrative Biology, Obstetrics and Gynecology Hospital of Fudan University, Fudan University, Shanghai 200438, China.
² State Key Laboratory for Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, Key Laboratory of Analytical Chemistry, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
³ Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
⁴ Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China.
⁵ Institute of Molecular Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China.
⁶ Institute of Cell Biology and Biophysics, Leibniz University Hannover, Hanover, Germany.

Abstract

Background: Serous borderline ovarian tumour (SBOT) is the most common type of BOT. Fertility sparing surgery (FSS) is an option for patients with SBOT, though it may increase the risk of recurrence. The clinical and molecular features of its recurrence are important and need to be investigated in detail.

Methods: An internal cohort of 319 patients with SBOT was collected from Aug 1, 2009 to July 31, 2019 from the Obstetrics and Gynecology Hospital of Fudan University in China. An external cohort of 100 patients with SBOT was collected from Aug 1, 2009 to Nov 30, 2019 from the Shandong Provincial Hospital in China. The risk factors for the recurrence were identified by multivariate cox analysis. Several computational methods were tested to establish a prediction tool for recurrence. Whole genome sequencing, RNA-seq, metabolomics and lipidomics were used to understand the molecular characteristics of the recurrence of SBOT.

Findings: Five factors were significantly correlated with SBOT recurrence in a Han population: micropapillary pattern, advanced stage, FSS, microinvasion, and lymph node invasion. A random forest-based online recurrence prediction tool was established and validated using an internal cohort and an independent external cohort for patients with SBOT. The multi-omics analysis on the original SBOT samples revealed that recurrence is related to metabolic regulation of immunological suppression.

Interpretation: Our study identified several important clinical and molecular features of recurrent SBOT. The prediction tool we established could help physicians to estimate the prognosis of patients with SBOT. These findings will contribute to the development of personalised and targeted therapies to improve prognosis.

Funding: JL was funded by MOST 2020YFA0803600, 2018YFA0801300, NSFC 32071138, and SKLGE-2118 to Jin Li; JY was funded by the Initial Project for Young and Middle-aged Medical Talents of Wuhan City, Hubei Province ([2014] 41); HH was funded by MOST 2019YFA0801900 and 2020YF1402600 to He Huang; JS was funded by NSFC 22,104,080; CG was funded by Natural Science Foundation of Shanghai 20ZR1408800 and NSFC82171633; BL was funded by Natural Science Foundation of Shanghai 19ZR1406800.

Keywords: Immunological suppression; Prediction model; SBOT.