Project description:Invasive malignant pleomorphic adenoma (IMPA) results from the malignant transformation of pleomorphic adenoma (PA). The former is a high-grade malignant tumor, whereas the latter is a benign opposite. Study on the molecular mechanism in the progression of PA to IMPA will be of benefit to elucidate the reasons for different biological behaviors among these salivary gland tumors with the same origin. But there is no valuable and non-invasive biomarker to screen IMPA currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary mRNAs (mRNA) can act as a biomarker to detect IMPA.
Project description:Pleomorphic adenoma (PA), the most common benign salivary gland tumor, presents unpredictable risks of recurrence and malignant transformation into carcinoma ex pleomorphic adenoma (CXPA), posing significant clinical challenges. To better delineate the tumor progression trajectory, we performed single-cell RNA sequencing on normal salivary glands, primary PA, recurrent PA (rPA), and CXPA, integrating cell trajectory reconstruction, differential gene expression analysis, and key gene network exploration to uncover molecular transitions and intercellular crosstalk underlying PA recurrence and malignant transformation. Our findings revealed GALNT13⁺ myoepithelial cells as CXPA-specific malignant progenitors, marking early malignant conversion, while MIF⁺ myoepithelial cells exhibited enhanced tissue-destructive capabilities. Fibroblasts played dual roles, enforcing fibrotic restraint in primary PA and promoting extracellular matrix degradation in CXPA. The tumor microenvironment demonstrated stage-specific adaptations, with CXPA favoring pro-inflammatory MIF–CD74/CD44 signaling, whereas rPA adopted immunosuppressive characteristics. Together, stromal reprogramming and immune-editing dynamics orchestrated microenvironmental adaptation, linking cellular heterogeneity to clinical aggressiveness. This study presents the first comprehensive molecular atlas of PA progression, highlighting the malignant specialization of myoepithelial subpopulations, fibroblast-mediated stromal remodeling, and immune-driven microenvironmental evolution, offering a valuable framework for precision stratification of malignant potential and future microenvironment-targeted therapeutic strategies.
Project description:Salivary gland tumors (SGTs) are a rare and heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The most common SGT subtype, pleomorphic adenoma (PA), can undergo malignant transformation into carcinoma ex pleomorphic adenoma (CXPA). Carcinomatous transformation from PA to CXPA is a highly progressive and multi-step process. Distinguishing a PA with some atypia from a low-grade intracapsular or minimally invasive CXPA is primarily subjective as no mitotic count thresholds exist to help pathologists distinguish between them in difficult cases. In this prospective study, we collected 140 cases encompassing both PA and CXPA to study their molecular signatures. The primary objective was to investigate the use of DNA methylation profiling as a potential molecular tool for differentiating between these two entities. Methylation analysis was performed on 33 PA cases and 33 CXPA cases. We were able to demonstrate that based on their methylation profiles, PA and CXPA could be classified into three distinct clusters that we called benign, intermediate, and malignant. We also revealed that the presence of TP53, HRAS, PTEN and/or TERT pathogenic mutations were exclusively present in CXPA cases; and that chromosomal alteration on chromosomes 5 and 8 are potentially associated with malignant transformation. In conclusion, our study provides a comprehensive molecular framework for PA and CXPA. The presence of a pathogenic mutation in TP53, HRAS, PTEN, or pTERT or HER2 amplification could be integrated into a molecular diagnosis of CXPA for tumors within the PA CXPA spectrum. In the future, we aim to improve our methylomic classification to make it a precision medicine diagnostic tool for the treatment management of tumors within the PA-CXPA spectrum.
Project description:N6-methyladenosine (m6A) is one of the most popular RNA modifications, which is widely found in messenger RNAs (mRNAs) .In our study,we provide m6A profiles of human invasive malignant pleomorphic adenoma, which open an avenue for in-depth knowledge and understanding of m6A topology in invasive malignant pleomorphic adenoma.
Project description:Here, we performed single cell RNA sequencing (scRNA-seq) analysis for 27, 810 cells from 2 donors with primary salivary gland pleomorphic adenoma
