SOXs: Master architects of development and versatile emulators of oncogenesis

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189295 - 189295

Published: March 1, 2025

Language: Английский

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Utility of SOX17 Immunohistochemical Stain in Serous Fluid Cytology Cell Block Specimens

Diagnostic Cytopathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

ABSTRACT Background The identification of metastatic tumors in serous fluid cytology specimens (SFCS) has always been a challenge. In this study, we explored SOX17 as an immunohistochemical (IHC) marker for the diagnosis gynecologic body specimens. Methods We selected 97 tumor cases, including 85 SFCS with adequate cell block material (from primary, n = 30 and others, 55) 12 histology (thymic thyroid tumors). IHC was performed on all results were interpreted positive or negative. Positive further characterized by intensity (nuclear staining) weak (1+), moderate (2+), strong (3+) percentage cells focal (< 10%), patchy (10%–50%) diffuse (> 50%). Results primary tumors, exhibited nuclear staining 28 out two cases showing staining. All non‐gynecologic effusion SOX17‐negative except one case renal carcinoma, which displayed pattern. consisting thymic negative SOX17. Conclusions tract origin positive, while other case. This finding suggests that is excellent addition to panel working up at sites, specifically when are differential diagnosis.

Language: Английский

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SOX17 is a highly sensitive and specific marker for metastatic ovarian and endometrial carcinomas in cytology cell block specimens

Cancer Cytopathology, Journal Year: 2023, Volume and Issue: 131(7), P. 465 - 470

Published: May 17, 2023

Abstract Background SOX17 (SRY‐box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian endometrial carcinomas in surgical specimens. In this study, validation of the utility immunohistochemistry (IHC) diagnosing metastatic gynecologic cytology specimens sought. Methods The study cohort included 84 cases that 29 (24 high‐grade serous carcinomas, two one low‐grade carcinoma, clear cell endometrioid carcinoma) 55 nongynecologic (10 renal 10 papillary thyroid 11 gastrointestinal adenocarcinomas, breast lung four urothelial carcinomas). Cytology specimen types peritoneal fluid ( n = 44), pleural 25), fine‐needle aspiration 15). IHC performed on block sections. intensity staining percent positivity tumor cells were evaluated. Results expressed all tested with diffuse strong nuclear expression (29 29; 100%). negative other (54 55; 98.18%) except carcinoma showed low (<10%). Conclusions is (100%) (98.2%) differential diagnosis Therefore, should be workup

Language: Английский

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Single-nuclei sequencing of uterine serous carcinoma reveals racial differences in immune signaling

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(34)

Published: Aug. 12, 2024

Significant racial disparities exist between Black and White patients with uterine serous carcinoma (USC). While the reasons for these are unclear, several studies have demonstrated significantly different rates of driver mutations groups, including TP53. However, limited research has investigated transcriptional differences tumors or composition tumor microenvironment (TME) groups. Here, we report single-nuclei RNA-sequencing profiles primary USC from diverse backgrounds. We find that there significant patients. Tumors exhibited higher expression specific genes associated aggressiveness, such as PAX8, axon guidance synaptic signaling pathways. also T cell populations reduced in tissue compared to matched benign, while anti-inflammatory macrophage retained within TME. Furthermore, connection PAX8 overexpression immunosuppression through regulation cytokines chemokines. Notably, show activity can influence gene protein secretion. These provide a detailed understanding transcriptome TME, identify biology

Language: Английский

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PAX8 in the Junction between Development and Tumorigenesis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7410 - 7410

Published: July 3, 2022

Normal processes of embryonic development and abnormal transformation to cancer have many parallels, in fact aberrant cell capabilities are traits restored a distorted, unorganized way. Some these autonomous, such as proliferation resisting apoptosis, while others involve complex interplay with other cells that drives significant changes neighboring cells. The correlation between is driven by shared proteins. proteins disappear after embryogenesis adult differentiated cancer, retained cells, acquiring new functions upon cancer. Many factors embraced transcription factors; some master regulators play major role determining fate. paired box (PAX) domain family developmental includes nine members involved differentiation various organs. All different types carrying pro-tumorigenic or anti-tumorigenic roles. This review focuses on PAX8, regulator the thyroid, kidney, male female genital tracts. We detail PAX8 each organ systems, describe its during if known, highlight cancers emerge from expressing

Language: Английский

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Precision-engineered biomimetics: the human fallopian tube

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 7, 2023

Abstract The fallopian tube has an essential role in several physiological and pathological processes from pregnancy to ovarian cancer. However, there are no biologically relevant models study its pathophysiology. state-of-the-art organoid model been compared two-dimensional tissue sections molecularly assessed providing only cursory analyses of the model’s accuracy. We developed a novel multi-compartment human that was meticulously tuned reflect compartmentalization heterogeneity tissue’s composition. validated this organoid’s molecular expression patterns, cilia-driven transport function, structural accuracy through highly iterative platform wherein organoids three-dimensional, single-cell resolution reference map healthy, transplantation-quality tube. This precision-engineered match microanatomy. One sentence summary Tunable modeling CODA architectural quantification tandem help design tissue-validated model.

Language: Английский

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SOX17 expression in mesonephric‐like adenocarcinomas and mesonephric remnants/hyperplasia of the female genital tract: Expanding its utility as a Müllerian biomarker

Histopathology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 8, 2024

Aims Recently, SOX17 has emerged as a promising biomarker for non‐mucinous Müllerian (ovarian and endometrial) carcinomas, demonstrating increased specificity in comparison to PAX8 while maintaining similar sensitivity. However, expression of mesonephric‐like adenocarcinoma (MLA), carcinoma the female genital tract with uncertain, but probably histogenesis, remains unexplored. This study aims address this gap. Methods results immunohistochemistry was performed on whole tissue sections from 68 MLAs originating endometrium or ovary seven cervical mesonephric well six remnants/hyperplasias. Using four‐tiered scoring system based distribution intensity staining, 68% MLA displayed negative/low (< 10%) pattern, which contrasts high observed most carcinomas. 22% demonstrated expression, other endometrial ovarian Similarly, five (72%) carcinomas cervix were SOX17‐negative, two cases (28%) positive. All remnants/hyperplasias negative. Conclusions The majority are negative exhibit low contrast diffuse strong commonly seen types carcinoma. subset demonstrate expression. Therefore, absence staining is supportive when differential includes another may also be useful differentiating malignancies benign glandular lesions.

Language: Английский

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Combined assembloid modeling and 3D whole-organ mapping captures the microanatomy and function of the human fallopian tube

Science Advances, Journal Year: 2024, Volume and Issue: 10(39)

Published: Sept. 27, 2024

The fallopian tubes play key roles in processes from pregnancy to ovarian cancer where three-dimensional (3D) cellular and extracellular interactions are important their pathophysiology. Here, we develop a 3D multicompartment assembloid model of the tube that molecularly, functionally, architecturally resembles organ. Global label-free proteomics, innovative assays capturing physiological functions (i.e., oocyte transport), whole-organ single-cell resolution mapping used validate these assembloids through multifaceted platform with direct comparisons tissue. These techniques converge at unique combination parameters highest similarity reference tube. This work establishes (i) an optimized human for vitro studies pathophysiology (ii) iterative customized models organs microanatomically accurate by combining tunable tissue methods.

Language: Английский

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PAX8 as a Potential Target for Ovarian Cancer: What We Know so Far

OncoTargets and Therapy, Journal Year: 2022, Volume and Issue: Volume 15, P. 1273 - 1280

Published: Oct. 1, 2022

Abstract: The Fallopian tube epithelium harbors the origin cells for majority of high-grade serous ovarian carcinomas (HGSCs), most lethal form gynecologic malignancies. PAX8 belongs to paired-box gene family transcription factors and it is a marker FTE secretory cell lineage. Its role has been investigated in migration, invasion, proliferation, survival, stem maintenance, angiogenesis tumor growth. In this review, we focus on pro-tumorigenic cancer; context, possibly continues exert its transcriptional activity physiological targets but may also function newly available after tumorigenic hits. Acquiring new insights into different mechanism(s) action microenvironment could uncover viable therapeutic thus improve current treatment regimen. Keywords: PAX8, cancer, factor, tube, STICs

Language: Английский

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Pan-cancer Analysis Reveals Cancer-dependent Expression of SOX17 and Associated Clinical Outcomes

Cancer Genomics & Proteomics, Journal Year: 2023, Volume and Issue: 20(5), P. 433 - 447

Published: Jan. 1, 2023

SRY-box containing gene 17 (SOX17) plays a pivotal role in cancer onset and progression is considered potential target for diagnosis treatment. However, the expression pattern of SOX17 its clinical relevance remains unknown. Here, we explored relationship between drug response by examining patterns across multiple types.Single-cell bulk RNA-seq analyses were used to explore profile SOX17. Analysis results verified with qPCR immunohistochemistry. Survival, response, co-expression performed illustrate correlation outcomes.The revealed that abnormal highly heterogenous types, indicating manifests as type-dependent feature. Furthermore, also associated prognosis certain types. Strong correlates potency small molecule drugs affect PI3K/mTOR signaling. FGF18, relevant SOX17, involved PI3K-AKT signaling pathway. Single-cell analysis demonstrated mainly expressed endothelial cells barely other but spreads cell types during development ovarian cancer.Our study pan-cancer through single-cell determined related diagnosis, staging, some tumors. These findings have implications may help identify mechanistic pathways amenable pharmacological interventions.

Language: Английский

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