Abstract A022: Multi-omics integration reveals TSPAN1 as a highly specific biomarker for early non-invasive diagnosis of ovarian cancer

Abstract Background: Ovarian cancer is the most lethal gynecologic malignancy worldwide. The high mortality is primarily attributed to the lack of specific symptoms in early stages, resulting in most patients being diagnosed at advanced stages and missing the optimal treatment window. Currently, CA125 combined with imaging is widely used for early screening and diagnosis, but its sensitivity and specificity remain limited. Therefore, there is an urgent need to identify more sensitive and specific non-invasive biomarkers to improve early detection and prognosis in ovarian cancer. Purpose: This study aims to identify novel ovarian cancer biomarkers through integrative multi-omics analysis that are both tumor tissue-specific and stably detectable in plasma, in order to overcome the current limitations in diagnostic sensitivity and specificity and enhance the potential for early screening and diagnosis. Methods: We conducted proteomic analysis of plasma and plasma-derived exosomes from patients with ovarian cancer and ovarian cysts using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In parallel, we integrated publicly available single-cell transcriptomic and spatial proteomic datasets to investigate the tissue origin and cell-type specificity of differentially expressed proteins. Candidate biomarkers were further compared with classical tumor markers such as CA125 and HE4 to identify those with superior potential for early diagnosis. Results: Proteomic analysis identified multiple differentially expressed proteins between ovarian cancer and cyst groups, among which TSPAN1 was significantly upregulated in the cancer group and showed the highest differential expression. Single-cell transcriptomic data revealed that TSPAN1 was predominantly expressed in malignant epithelial cell clusters, but showed low or undetectable expression in normal epithelial and stromal cells. Spatial proteomic analysis further confirmed the tumor-specific localization of TSPAN1 in ovarian cancer tissues. In an independent validation cohort, ELISA assays showed significantly elevated TSPAN1 levels in the plasma of ovarian cancer patients (P < 0.001). ROC analysis demonstrated an AUC of 0.92 for TSPAN1, compared to 0.81 for CA125, suggesting superior sensitivity and specificity. Additionally, we found that TSPAN1 levels were higher in chemoresistant ovarian cancer patients than in chemosensitive ones, indicating a potential association with poor prognosis. Conclusion: By integrating multi-omics data, this study identified TSPAN1 as a tumor-specific biomarker for ovarian cancer with strong potential for early detection and non-invasive diagnosis. TSPAN1 may complement CA125 in clinical practice and could be applied for early screening and high-risk population identification. Further validation in larger patient cohorts is warranted. Citation Format: Chang Lei, Yamin Zhao. Multi-omics integration reveals TSPAN1 as a highly specific biomarker for early non-invasive diagnosis of ovarian cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A022.