Azam, Zulfikar Zhang, Xiaojun Wahab, Riajul Hasan, Md Mahedi Dhadhal, Shivaniben Kang, Bowon Hassan, Md Mynul Karim, Mazharul Choi, Jeong Uk Rana, Muhit Zhang, Jian-Ying Roy, Sourav Byun, Youngro Kim, In-san Song, Jae Yun Toy, Eugene P. Reddy, Sireesha Y. Alam, Farzana Al-hilal, Taslim A. 2025-12-19T07:01:49Z 2025-12-19T07:01:49Z 2025-12-19 2026-03 0020-7136 https://pubs.kist.re.kr/handle/201004/153809 Detecting ovarian cancer (OC) early using existing biomarkers, for example, cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion-like protein, expresses in the male reproductive organ but is absent in female reproductive systems and healthy tissues, but plays an important role in neo-angiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed in circulating tumor cells (Dpl+CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased levels of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as an OC-specific biomarker. Serum Doppel levels can distinguish OC with high sensitivity and specificity (sensitivity = 0.91 and specificity = 0.89) and can also detect early-stage HGSOCs (FIGO stages I and II) from non-cancerous conditions with high sensitivity and specificity (sensitivity = 0.94 and specificity = 0.83). Moreover, significantly higher Doppel expression is observed in all EOC subtypes except clear cell OC. Stratifying the EOCs based on Doppel levels, we categorized them into Doppel-high (Dplhi) and Doppel-low (Dpllow) groups. Using ascites-derived organoids, made from Dplhi and Dpllow patients, we identify that Doppel induces epithelial–mesenchymal transition (EMT). Doppel levels in the sera/ascites correlate with the changes in Dpl+CTC number in whole blood, highlighting the association of Doppel-induced EMT with CTC dissemination in the circulation. Thus, Doppel-based detection of EOC subtypes could be a promising platform as a clinical biomarker and link the Doppel axis with OC dissemination. English John Wiley & Sons Inc. Doppel as an early-stage biomarker promoting EMT and dissemination in ovarian cancers Article 10.1002/ijc.70268 1 International Journal of Cancer, v.158, no.6, pp.1755 - 1768 International Journal of Cancer 158 6 1755 1768 Y scie scopus 001626573300001 2-s2.0-105023489419 Oncology Oncology Article EPITHELIAL-MESENCHYMAL TRANSITION PROTEIN DOPPEL CELLS EXPRESSION biomarker circulating tumor cells Doppel EMT organoids ovarian cancer