Comparing Ovarian Clear Cell Carcinoma and High-Grade Serous Carcinoma Based on the SEER Database and Analyzing the Significantly Mutated Genes.

Abstract

Introduction: Ovarian clear cell carcinoma (OCCC) accounts for about 5% of all epithelial ovarian cancers. Currently, its treatment mainly refers to high-grade serous carci-noma (HGSC). This study aimed to explore differences in clinical characteristics between OCCC and HGSC and studied the reasons for the differences.

Methods: The data of OCCC and HGSC cases were obtained from the SEER database. Uni-variate and multivariate Cox regression analyses were used to explore the prognostic factors. Next, whole exome sequencing (WES) was performed on 15 clinically selected OCCC cases and 16 HGSC cases to identify significantly mutated genes (SMGs). Further analysis included calculating tumor mutation burden (TMB) and predicting potential target drugs based on the identified mutations.

Results: 3493 OCCC and 10266 HGSC patients from the SEER database were included in the study. Survival analysis showed that the overall survival (OS) of stage I-II OCCC was better than that of stage I-II HGSC, while the OS of stage III-IV OCCC was worse than that of stage III-IV HGSC. Further subgroup analysis showed that for the OCCC group, age ≥ 60 years, bilateral tumor distribution, tumor size ≥ 87mm, and stage III-IV were independent risk factors for OS. For HGSC patients, tumor size ≥ 87mm was an independent protective factor for OS. WES results suggested that among the top 20 SMGs of OCCC in stage III-IV patients, DNAH2, LAMA5, MUC19, NOTCH1, PCLO, SYNE2, TACC2, and ZNF469 were 8 specific SMGs that distinguish III-IV OCCC from III-IV HGSC. In addition, the stage I-II OCCC group had the highest TMB, and the lowest was the stage III-IV OCCC.

Discussion: Our findings challenge the conventional uniform therapeutic approach for ovarian carcinomas by revealing stage-dependent SMGs between OCCC and HGSC. However, limi-tations such as the retrospective SEER analysis, small WES cohort, and population-specific driver gene variations require cautious interpretation of the findings.

Conclusions: The independent prognostic factors identified in this study provide a theoretical basis for individualized prognosis judgment in OCCC and HGSC. The SMGs and TMB levels may serve as valuable indicators for prognosis and evaluating targeted therapy or immunother-apy efficacy. Druggable genes such as NOTCH1 and RYR3 offer promising therapeutic tar-gets, while stage-specific pathway enrichments reveal potential intervention strategies. Further validation in larger cohorts is needed to confirm these findings. Our study advances the under-standing of molecular heterogeneity in ovarian cancer and lays the groundwork for personal-ized treatment strategies, ultimately improving patient outcomes.