Spatial transcriptomic analysis reveals coordinated gene expression in ovarian clear cell carcinoma and adjacent endometriosis in UK and Japanese patients

Kuroda, T.; Giannone, G.; Ennis, D. P.; Mirza, H. B.; Marks, D.; Flood, L.; Sisley, M.; Griffin, R.; Desai, S.; McDermott, J.; Lambie, N.; Fukasawa, N.; Kiyokawa, T.; Shimoda, M.; Saito, M.; Koba, T.; Saito, R.; Kawabata, A.; Takenaka, M.; Valabrega, G.; Matthews, N.; Tookman, L. A.; Yanaihara, N.; Okamoto, A.; McNeish, I. A.

doi:10.64898/2026.05.29.728698

Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.05.29.728698

Spatial transcriptomic analysis reveals coordinated gene expression in ovarian clear cell carcinoma and adjacent endometriosis in UK and Japanese patients

View original source ↗Export metadata ↓

Abstract

PurposeOvarian clear cell carcinoma (OCCC) is strongly associated with endometriosis and shows geographic variation in incidence. We investigated whether OCCC and adjacent endometriosis exhibit distinct transcriptional states and whether these patterns differ between United Kingdom (UK) and Japanese cohorts. Experimental DesignWe performed whole-transcriptome spatial profiling on specimens from 16 OCCC cases (8 UK, 8 Japan) in which tumor and endometriosis were both present. Gene expression was analyzed in tumor, endometriosis and stroma. ARID1A status was assessed by immunohistochemistry. ResultsMedian age was 59 years (range 26-82). 13/16 cases (81.3%) had early-stage disease. Tissue compartment rather than cohort of origin was the dominant source of variation across endometriosis and tumor regions. Endometriosis was enriched for inflammatory and immune-related pathways compared to tumor, whilst there was greater representation of chromatin and protein-DNA complex assembly pathways in tumor regions. These patterns were conserved across both cohorts and after stratification by ARID1A status. Mesenchymal-associated gene expression scores also significantly differed across stroma, endometriosis and tumor with clear compartmental separation. Cell type deconvolution analyses showed clear compositional differences between stromal and epithelial disease compartments. ConclusionsOCCC and coexisting endometriosis are transcriptionally distinct, with the dominant contrast being compartmental rather than geographic. ARID1A alone is unlikely to account for the principal spatial transcriptional states identified here. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between OCCC and coexisting endometriosis or represent different stages of endometriosis-associated tumorigenesis. Translational RelevanceOvarian clear cell carcinoma often arises in association with endometriosis, yet the biological transition between these lesions remains poorly understood. Using spatial transcriptomics in matched tumor and adjacent endometriosis from Japanese and UK cohorts, we showed that endometriosis is characterized by inflammatory and antigen-presentation features, whereas tumor regions showed chromatin-organization and oncogenic transcriptional states. These patterns were largely maintained irrespective of ARID1A status and geographic background. In addition, spatial deconvolution suggested differences in local immune composition, with tumor regions showing relatively greater neutrophil- and T cell-associated signals. Together, our data suggest that OCCC and coexisting endometriosis share a spatially linked tissue context, but that tumor regions have distinct transcriptional profile and microenvironment that may be involved in the malignant transformation and inform interpretation of molecular classification in endometriosis-associated OCCC.

Explore related subjects

pathology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Kuroda, T., Giannone, G., Ennis, D. P., Mirza, H. B., Marks, D., Flood, L., Sisley, M., Griffin, R., Desai, S., McDermott, J., Lambie, N., Fukasawa, N., Kiyokawa, T., Shimoda, M., Saito, M., Koba, T., Saito, R., Kawabata, A., Takenaka, M., Valabrega, G., Matthews, N., Tookman, L. A., Yanaihara, N., Okamoto, A., McNeish, I. A.. 2026-06-02. Spatial transcriptomic analysis reveals coordinated gene expression in ovarian clear cell carcinoma and adjacent endometriosis in UK and Japanese patients. https://doi.org/10.64898/2026.05.29.728698

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Prevention of Unc13a cryptic splicing is sufficient to preserve memory

TDP-43 dysfunction is thought to underlie frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, neurodegenerative dementias currently without effective therapy. Therapeutic strategies are designed to correct individual cryptic targets of TDP-43, such as UNC13A, whereby its cryptic splicing compromises synaptic function, yet the sufficiency of such an approach to prevent memory deficits is unclear. Using a forebrain neuron-specific TDP-43 knockout mouse model that recapitulates TDP-43 dysfunction occurring during early stages of human disorders, we found here that prevention of cryptic splicing to include that of Unc13a attenuated memory deficits. We show that genetic ablation of Unc13a cryptic exon solely in such TDP-43 knockout mice is sufficient to preserve cognition, supporting the clinical value of targeting UNC13A to mitigate memory deficits. Prevention of cryptic splicing of multiple targets of TDP-43 additionally attenuate neuron loss. For optimal outcomes in TDP-43 related dementias, these findings thus strongly support strategies designed to repress cryptic splicing of multiple targets of TDP-43, including UNC13A.

pathology↗

bioRxiv2026

Social-Cognitive Dysregulation Model of Misophonia: Perspective from a Behavioural Study

Misophonia is increasingly conceptualized as more than a disorder of sound tolerance, with trigger over-reactivity shaped by the social meaning of sounds, inferred intentions, and representations of others actions. We tested a social-cognitive dysregulation model of misophonia in (N = 341) adults using behavioural measures of Theory of Mind and emotion recognition, alongside measures of reflective functioning, empathy, alexithymia, and mimicry. Dimensional associations with misophonia severity and its five different dimensions were examined while accounting for age, sex, sound sensitivity, and anxiety/depressive symptoms. Increased misophonia severity was associated with less accurate and slower mental-state inference and emotion recognition. ToM accuracy effects were evident for more complex, cognitive, and affective mentalizing, but not for simpler mentalizing or physical control judgments, while emotion-recognition accuracy differences emerged for positive but not negative stimuli. Greater severity was also characterized by reduced certainty and greater uncertainty about mental states, greater difficulty identifying one s own feelings, and elevated alexithymia, whereas global self-reported empathy was largely preserved. Misophonia severity further predicted a greater propensity to mimic trigger-producing actions or sounds; 41% of participants exceeding the S-Five clinical cutoff (> 87) endorsed mimicry, which was particularly associated with a subjective restoration of control. Findings remained robust following influential-case sensitivity analyses. These results reveal a selective disturbance in self-other representation spanning mentalizing, emotion decoding, emotional self-representation, and embodied regulatory processes. They position misophonia within a broader social-cognitive framework in which auditory-affective reactivity may intersect with altered inferential and sensorimotor processing, while stopping short of causal inference.

pathology↗

bioRxiv2026

Lamin A/C depletion from myofibers and satellite cells in mice reveals selective muscle pathology

Mutations in the laminA/C gene (LMNA), which encodes the nuclear lamina proteins lamin A and lamin C (lamin A/C), have been linked to different human diseases affecting different tissues. Most LMNA mutations cause cardiomyopathy and muscular dystrophy, such as autosomal dominant Emery-Dreifuss muscular dystrophy. Recent studies to understand striated muscle laminopathies have taken advantage of Lmna conditional knockout mice to examine the effects of lamin A/C depletion in cardiomyocytes and cardiac fibroblasts. However, the role of lamin A/C in skeletal muscle has largely been uncharacterized using conditional knockout mice. We used different mouse lines to deplete lamin A/C from specific cell types in striated muscle. Lamin A/C depletion from fetal myofibers and cardiomyocytes led to no observable phenotype in the skeletal muscles despite leading to dramatic heart dilation and early lethality. Depletion of lamin A/C from both skeletal myofibers and satellite cells was lethal, with the most dramatic myopathic abnormalities observed in the intrinsic muscles of the tongue. The presence of lamin A/C in skeletal muscle satellite cells prevented the development of lethal myopathy when the proteins were deleted only from differentiated myofibers. Overall, our results provide a foundation for understanding the roles of lamin A/C in muscle maintenance and development, including the variable skeletal muscle involvement and much more invariant cardiomyopathy in patients with LMNA mutations.

pathology↗