Biology subjects

Chahoud, J.

Publications and source records attributed to Chahoud, J..

3 recordsLinked to original sources

bioRxiv2025

Tissue Factor Expression in Penile Squamous Cell Carcinoma: A Marker of HPV-Independent Disease

In a series of 33-patients, we evaluated tissue factor (TF) expression in penile squamous cell carcinoma (PSCC). A tissue microarray (TMA) was constructed with 3 cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry and H-scores for membrane and cytoplasm staining were assessed (range 0-300). Percentage of cores and patient tumors staining positive for TF ([≥]10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. Association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence free survival (RFS), and cancer specific survival (CSS) were assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data was determined in a similar manner. TF staining was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs 18.8; p=0.003) and cytoplasm (H-score 59.2 vs. 17.7, p=0.007). Cytoplasmic (H-score 61.7 vs 11.7, p=<0.001) and membrane TF staining (H-score 71.7 vs 15.0, p=<0.001) favored p16 negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs 18.3, p=0.012; membrane H-score 67.5 vs 20.3, p=0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p=0.052; cytoplasmic H-score 135 vs. 107.5, p=0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p=0.014; cytoplasmic H-score 110 vs. 93.3, p=0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this is due to our small sample size. Our results indicate that TF expression could be positive biomarker for HPV-independent, p53-aberrant PSCC, while TROP2 could be associated with HPV-associated PSCC.

pathology↗

bioRxiv2023

Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment

BackgroundImmunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naive and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples. Spatial gene set enrichment analysis (GSEA) and autocorrelation (coupling with high expression) of ligand-receptor transcript pairs were assessed. Multiplex immunofluorescence (mIF) validation was used for significant autocorrelative findings and the cancer genome atlas (TCGA) and the clinical proteomic tumor analysis consortium (CPTAC) databases were queried to assess bulk RNA expression and proteomic correlates. Results21 patient samples underwent SMI. Viable tumors following IO harbored more stromal CD8+ T cells and neutrophils than IO naive tumors. YES1 was significantly upregulated in IO exposed tumor cells. The epithelial-mesenchymal transition pathway was enriched on spatial GSEA and the associated transcript pair COL4A1-ITGAV had significantly higher autocorrelation in the stroma. Fibroblasts, tumor cells, and endothelium had the relative highest expression. More integrin V+ cells were seen in IO exposed stroma on mIF validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV. In CPTAC, collagen IV protein was more abundant in advanced stages of disease. ConclusionsOn spatial transcriptomics, COL4A1 and ITGAV were more autocorrelated in IO-exposed stroma compared to IO-naive tumors, with high expression amongst fibroblasts, tumor cells, and endothelium. Integrin represents a potential therapeutic target in IO treated ccRCC.

cancer biology↗

bioRxiv2021

Spatial Clustering of CD68+ Tumor Associated Macrophages with Tumor Cells is Associated with Worse Overall Survival in Metastatic Clear Cell Renal Cell Carcinoma

Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. SIGNIFICANCEIncreased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.

cancer biology↗