Biology subjects

Rovite, V.

Publications and source records attributed to Rovite, V..

4 recordsLinked to original sources

bioRxiv2026

Spatial organization of myofibroblastic and complement-secreting CAFs in neuroendocrine tumors

Neuroendocrine tumors are graded and classified largely by tumor cell-intrinsic features, yet the stromal microenvironment remains poorly defined across anatomical sites. We applied near single-cell spatial transcriptomics augmented with cell segmentation to eight treatment-naive neuroendocrine tumor primary tissues from pancreas, colon, appendix, and bile duct to build a spatially resolved stromal reference. Integration of stromal-enriched cell polygons identified ten transcriptional states shared across tumors, with a minority of niche-restricted clusters mapping to tumor/stroma and stroma/non-tumor boundaries. Within the shared fibroblast compartment, program scoring resolved four cancer-associated fibroblast states. Myofibroblastic and complement-secretory states dominated across samples, whereas inflammatory and antigen-presenting programs were consistently detected but weaker. Spatial mapping in desmoplastic tumors showed myofibroblastic fibroblasts enriched in collagen-dense regions, while complement-secretory fibroblasts localized preferentially to tumor-adjacent stromal interfaces. Pseudobulk differential expression and gene set enrichment analyses supported extracellular matrix remodeling in myofibroblastic fibroblasts and complement cascade activation in complement-secretory fibroblasts. Together, these findings demonstrate that anatomically distinct neuroendocrine tumors share a conserved yet spatially segregated stromal architecture, characterized by dominant matrix-producing and complement-enriched fibroblast states.

molecular biology↗

bioRxiv2025

Unveiling the Immune Landscape of COVID-19 and prolonged Long-COVID through Single-Cell RNA Sequencing

Long-COVID affects at least 10% of COVID-19 survivors, displaying debilitating symptoms across multiple organ systems. Despite the increasing prevalence, the underlying causes remain unclear. This study presents a unique analysis of the PBMC transcriptomic landscape of COVID-19 and Long-COVID patients at a single-cell resolution. We reconstructed the cell state and communication using differentially expressed gene profiling and ligand-receptor interaction analyses. Our results reveal altered T and NK cell subset proportions, diminished proliferating lymphocyte and B cell signalling capacity, and the expression of exhaustion and cytotoxicity associated genes 1.5 - 2 years post-infection, suggesting incomplete immune recovery. Collectively, these findings provide insights into the immune processes underlying the progression of COVID-19 into a chronic Long-COVID state.

immunology↗

bioRxiv2024

An integrative RNA spliceosomic landscape of pancreatic neuroendocrine tumors unveils novel clinicomolecular associations

Alterations in alternative splicing are emerging as a novel hallmark in cancer biology, offering new insights. However, integrative analyses of splicing are still scarce, particularly in rare cancers such as pancreatic neuroendocrine tumors (PanNETs). These tumors are highly heterogeneous, complicating diagnosis and treatment. This study is the first to comprehensively investigate the RNA splicing landscape in PanNETs, identifying distinct spliceosomic profiles correlated with unique clinical and molecular characteristics. We analyzed RNA-seq data from 174 samples, identifying three distinct spliceosomic groups (SPN1, SPN2, SPN3) with unique clinical and molecular characteristics. SPN1 exhibited intermediate clinical features and specific splicing machinery profile, SPN2 was associated with frequent mutations in MEN1 and DAXX/ATRX genes, and SPN3 showed a prevalence of well-differentiated tumors with distinct splicing patterns. These groups were linked to different clinical outcomes and activated key biological processes like mTOR signaling and hormone secretion pathways. Our findings underscore the significant impact of RNA splicing on PanNET heterogeneity and suggest that detailed splicing profiles could serve as valuable tools for identifying novel biomarkers and therapeutic targets. This study provides crucial insights into PanNET molecular biology and paves the way for personalized therapies based on splicing features.

cancer biology↗

bioRxiv2023

Digital spatial profiling of RNA in pancreatic neuroendocrine tumors highlights the distinct profile of alpha-SMA positive stroma and its impact on surrounding tumor cells

ObjectiveAlpha smooth muscle actin (-SMA) expression in stroma is linked to the presence of cancer-associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a digital spatial profiling approach, we characterized the gene expression profiles of the tumor and -SMA positive stromal cell compartments in pancreatic neuroendocrine tumor (PanNET) tissues. MethodsThe profiling was performed in tissues from eight retrospective cases (Three Grade 1, four Grade 2, and one Grade 3) where the segmentation was done based on tissue morphology and synaptophysin (tumor), -SMA (stroma) marker expression. ResultsThe stromal cell-associated genes were mainly involved in pathways of extracellular matrix modification, while in tumor cells, the gene expression profiles were primarily associated with the pathways involved in cell proliferation. The comparison of gene expression profiles across all three PanNET grades revealed that heterogeneity is not only present within the tumor but also in the -SMA positive stromal cells. Furthermore, the comparison of tumor cells adjacent versus non-adjacent to -SMA positive stromal cells revealed an upregulation of MMP9 in G3 tumor analysis. ConclusionsOverall, this study provides an in-depth characterization of gene expression profiles in both stroma and tumor cells of PanNETs and outlies potential crosstalk mechanisms.

cancer biology↗