Biology subjects

Martorana, A.

Publications and source records attributed to Martorana, A..

4 recordsLinked to original sources

bioRxiv2026

Integrated transcriptomic analysis identifies Paternally Expressed Gene 10 as a novel candidate biomarker associated with aggressive features in liposarcoma

Abstract Background Liposarcoma is a rare cancer, comprising four major histological subtypes: well-differentiated, dedifferentiated, myxoid and pleomorphic liposarcoma. Therapeutic options remain limited for advanced disease, and additional biomarkers that may support biological characterization, diagnosis, or risk stratification are needed. Methods Bulk RNA sequencing (RNA-seq) was performed on paired tumour and adjacent non-tumour tissues from an analysable subset of 16 patients (22 tumour specimens) within a clinicopathological cohort of 21 patients. Differential gene expression analysis, principal component analysis, gene set enrichment (GSEA) analysis and single-sample GSEA (ssGSEA) were used to define subtype-specific transcriptional programs and imprinted-gene dysregulation. PEG10 expression was validated by RT-qPCR and RNA fluorescence in situ hybridization (FISH), and its cellular localization was explored by combined FISH and immunofluorescence for P53, vimentin, Ki67, and CD34. PEG10 expression in liposarcoma was further investigated in an external single-cell RNA-sequencing dataset of dedifferentiated liposarcoma. An exploratory survival analysis was performed in the pan-sarcoma TCGA-SARC cohort. Results Transcriptomic profiling identified distinct subtype-specific gene expression patterns and broad dysregulation of imprinted genes in liposarcoma compared with adjacent non-tumour tissue. Among all the imprinted genes, PEG10 showed a marked tumour-to-normal expression difference and good discriminatory performance between tumour and normal tissues in the discovery cohort (AUC=0.867). In the TCGA sarcoma cohort high PEG10 expression was associated with shorter overall survival. Immuno-FISH and single-cell analyses revealed that PEG10 was predominantly detected in tumour and proliferating cell populations. Importantly, PEG10 expression was higher in high-grade tumours. In bulk RNA-seq data, PEG10 expression correlated with hypoxia, extracellular matrix remodelling and invasion ssGSEA signatures. In the external single-cell RNA-seq dataset PEG10high tumours showed a reduced immune cell infiltration. Conclusions This study provides an integrated transcriptomic characterisation of liposarcoma and identifies PEG10 as a candidate tumour-associated biomarker linked to aggressive disease features. The diagnostic and prognostic value of PEG10 requires validation in larger, independent, subtype-balanced liposarcoma cohorts, and its potential therapeutic relevance requires direct functional investigation.

genomics↗

bioRxiv2025

A novel peptidoglycan deacetylase modulates daughter cell separation in E. coli

Peptidoglycan hydrolases facilitate bacterial cell wall growth by creating space for insertion of new material and allowing physical separation of daughter cells. In Escherichia coli, three peptidoglycan amidases, AmiA, AmiB and AmiC, cleave septal peptidoglycan during cell division. The LytM-domain proteins EnvC and NlpD activate these amidases either from inside the cell or the outer membrane: EnvC binds to the cytoplasmic membrane-anchored divisome components FtsEX, and NlpD and ActS are outer membrane lipoproteins. Here we report the identification of a novel periplasmic deacetylase called SddA that removes acetyl groups from denuded peptidoglycan glycan strands, the products of amidases. SddA is a substrate for the periplasmic protease Prc, suggesting regulation via protein degradation. The sddA gene is co-expressed with the gene encoding EnvC, linking SddA function to amidase activation. Consistent with this link, the deletion of sddA alleviates phenotypes associated with lack of amidase activation, while overexpression of sddA alleviates phenotypes related to a defective Tol-Pal system and causes cell chaining due to reduced septum peptidoglycan cleavage unless envC is co-expressed. We present a model according to which SddA modulates the activation of the septum-splitting amidases during cell division. AUTHOR SUMMARYBacteria surround their cell membrane by the essential peptidoglycan (cell wall) layer to prevent bursting open due to their turgor. During cell division, bacteria produce a septum at midcell, which must be cleaved for daughter cells to separate. Here, we report the identification of a new enzyme, SddA, that modifies a particular type of peptidoglycan material, denuded glycan chains released during the splitting of septal peptidoglycan for daughter cell separation, in the Gram-negative Escherichia coli. We propose a model in which SddA modulates a switch in the septal peptidoglycan splitting, ensuring splitting is activated from the cell membrane in the early stages of cell division and from the outer membrane in the late stages.

microbiology↗

bioRxiv2023

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis

Endometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. Incomplete surgery often results in recurring symptoms and the need for additional interventions. This study aims to explore the biological significance of PARP-1, EpCAM, and FR as potential targets for molecular imaging in endometriosis, assessing their suitability for targeted intraoperative imaging. Gene expression analysis was performed using the EndometDB. By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FR in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis image to perform a quantitative immunolocalization analysis. Additionally, double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as PARP-1 and FR, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment. The analysis of gene expression revealed that PARP-1, EpCAM, and FR exhibit higher levels of expression in endometriotic lesions compared to the peritoneum, used for control tissue. Immunohistochemical analysis also highlighted a significant increase in expression of all three biomarkers in endometriosis foci compared to surrounding tissues, as well as the quantitative analysis of immunolocalization of the signal. Furthermore, the double immunofluorescence analysis consistently revealed nuclear expression of PARP-1 and membrane and cytoplasmatic expression of EpCAM and FR, although relatively weaker. Overall, the three markers demonstrate significant potential for effective imaging of endometriosis. Particularly, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.

cell biology↗

bioRxiv2020

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

The pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. This study offers an opportunity for novel therapeutic intervention in EM, a difficult to treat gynecological condition. SummaryC3 produced by the endometriotic tissue is involved in the lesion development through mast cell activation

immunology↗