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Introduction
Ovarian cancer is one of the most common gynecological malignancies and remains a frequent cause of cancer-related death among women worldwide. According to statistics from the International Agency for Research on Cancer, ovarian cancer accounted for 3.4% of all newly diagnosed cancer cases and 4.8% of cancer-related deaths worldwide in 2022. It is the eighth most common cancer among women and the second most frequent gynecological malignancy [1].The challenge in early diagnosis, combined with its heterogeneous nature, contributes to poor prognosis. Even within epithelial ovarian cancer, the most prevalent subtype, there are five major histotypes that exhibit distinct clinical and genetic characteristics [2]. This heterogeneity extends beyond tumor cells to the complex tumor microenvironment, which plays a crucial role in disease progression and treatment response.
Understanding this heterogeneity at the molecular level requires advanced analytical approaches such as single-cell RNA sequencing (scRNA-seq). This technology enables the detailed examination of individual cells within the tumor microenvironment, revealing cell-specific gene expression patterns and regulatory mechanisms that may be masked in bulk tissue analyses [3, 4]. Through scRNA-seq, researchers can identify distinct cell populations and their unique molecular signatures, providing insights into the complex cellular interactions within the tumor ecosystem.
Protein post-translational modifications, particularly ubiquitination and deubiquitination, are emerging as critical regulators of cellular processes in cancer. Ubiquitination, a common post-translational modification, plays an essential role in protein degradation and cellular metabolism [5, 6]. It regulates key biological processes such as cell cycle progression, DNA repair, and cell signaling pathways. Conversely, deubiquitination, the process of removing ubiquitin chains from proteins, is equally vital for maintaining normal cellular function and homeostasis [7]. The dynamic balance between ubiquitination and deubiquitination has been implicated in various aspects of cancer biology, including tumor initiation, progression, and drug resistance. Recent evidence suggests that deubiquitinating enzymes (DUBs) may have cell type-specific functions within the tumor microenvironment, potentially influencing both cancer cells and stromal components. However, the precise role of deubiquitination in different cell populations within ovarian cancer remains poorly understood. By integrating scRNA-seq analysis with deubiquitination pathway studies, we can better understand how these molecular mechanisms contribute to ovarian cancer heterogeneity and progression, potentially identifying new therapeutic targets and strategies.
With the rapid accumulation of high-throughput sequencing technologies and multi-omics data, machine learning...