Marwa Hamdan

Background: Pulmonary endothelial cells are increasingly recognized as active regulators of organ-specific metastasis; however, the mechanisms by which they influence melanoma invasion remain incompletely understood. Methods: Six primary melanoma-derived cell lines were first assessed for their invasive responses to HPMEC-conditioned medium. In a separate HPMEC co-culture invasion model, invasive and non-invasive melanoma subpopulations were isolated and analyzed for the expression of 88 chemokine and cytokine receptor genes. Candidate receptors were subsequently validated in primary melanoma tissues (n = 15), while their corresponding ligands were analyzed in patient plasma samples (n = 30). Results: HPMEC-conditioned medium enhanced invasion in half of the melanoma cell lines. Exploratory receptor-expression analyses identified candidate genes, including CCR2, IL11RA, IL15RA, TNFRSF11B, and TNFRSF12A, with expression patterns potentially associated with the observed invasive responses, while CCR4 expression was consistently elevated in all invasive subpopulations. In an exploratory analysis of a small primary melanoma tissue cohort, CCR2 and TNFRSF11B expression was significantly higher in tumors from patients with lung metastases, while IL11RA expression was upregulated compared with that in non-metastatic tumors. Melanoma cells consistently induced endothelial IL-8 expression, whereas plasma concentrations of the corresponding ligands did not differ significantly between patient groups. Conclusions: The elevated expression of CCR2, IL11RA, and TNFRSF11B observed in primary melanomas associated with lung metastases suggests that these factors may contribute to the development or progression of pulmonary metastases. These findings highlight the potential role of bidirectional communication between endothelial cells and melanoma cells in metastatic progression.

Background: The metastatic dissemination of melanoma involves adhesion of circulating tumor cells within organ-specific vascular beds; however, the relative contribution of the endothelial environment versus that of the melanoma-intrinsic molecular state remains unclear. Materials and Methods: We quantified the in vitro adhesion of primary (n = 5) and metastatic (n = 3) melanoma cell lines to human hepatic, brain, and pulmonary endothelial cells under co-culture conditions, and we profiled the expression of 86 adhesion- and extracellular-matrix-related genes in melanoma and endothelial cells. Results: Adhesion was highest for the hepatic endothelium, intermediate for the pulmonary endothelium, and lowest for the brain endothelium. This endothelial preference was conserved in both primary and metastatic melanoma cells, though metastatic cells exhibited higher absolute adhesion. The linear mixed-effect models revealed that the effects of adhesion state on melanoma gene expression were modest and varied by endothelial type, whereas melanoma origin had more widespread and larger effects (mean absolute standardized coefficients of 0.32–0.47 versus 0.60–0.87, respectively). The expression of three genes (SPP1, ITGA11, and MMP2) was associated with melanoma origin in all endothelial types. Spearman’s co-expression analysis revealed endothelial-type-specific gene networks, and within-sample permutation confirmed the non-random coordination in all three endothelial types. Conclusions: Our findings support a model in which endothelial organ specificity contributes to melanoma cell adhesion behavior and associated transcriptional patterns, highlighting the importance of the vascular interface as a biologically active mediator of early metastatic cell–endothelium interactions.

Solid tumors retain transcriptional programs inherited from their tissue of origin, but the degree of this retention has not been quantified as a continuous metric, nor has its prognostic relevance been evaluated systematically. We developed the Tissue Memory Score (TMS) by projecting tumor bulk RNA-seq onto principal component axes constructed from 2,694 Genotype-Tissue Expression V8 samples across eight healthy tissues, and applied it to 3,900 primary tumors from eight Cancer Genome Atlas cohorts. Nearest-centroid classification recovered tissue identity in six of eight tumor types (80.1%-100.0% accuracy; chance 12.5%; all p < 10⁻⁵⁵). The two failures, gastric and endometrial carcinoma, reflected limitations of the reference atlas composition and not loss of tissue memory. Among cohorts passing pre-specified retention and dedifferentiation gates, TMS was independently associated with overall survival in clear cell renal cell carcinoma (ccRCC; multivariable HR = 0.59 per SD; 95% CI 0.46-0.77; p = 6.6 × 10⁻⁵) and accounted for 16.3% of explained survival variance by Shapley decomposition. The association held under purity residualization, rank transformation, stage stratification, and progression-free interval as an alternative endpoint. In hepatocellular carcinoma, TMS showed a protective univariable association in the same direction, which did not survive multivariable adjustment and is reported as exploratory. External application to CPTAC-ccRCC yielded a pooled hazard ratio of 0.71 in the same direction (I² = 0%). Tissue-of-origin transcriptional memory is quantifiable in solid tumors and independently prognostic in ccRCC, but did not extend to the remaining seven cohorts. Broader applicability depends on whether the reference atlas represents the cellular compartment from which a given carcinoma arises.

In this research, we aimed to study the diagnostic value of serum ferritin in assessing iron status in hemodialysis patients (HD). While ferritin is one of the most important laboratory parameters used to assess iron status, but the presence of confounding factors such as chronic inflammation in HD patients may confuse the interpretation of laboratory results. The study was conducted on 73 adult patients who were on maintenance HD at Al-Basel Hospital in Homs, Syria, with the presence of 25 age-matched healthy subjects. Blood samples were collected before the HD session, serum CRP was used as an inflammatory marker. The results showed a significant increase in serum ferritin values in the patients group compared to healthy subjects, with an average value of (539.64 ng/ml), and this increase coincided with a decrease in Hb and TSAT values, but with an increase in CRP. Also, we found a significant positive correlation between ferritin and CRP (r2 = 0.132, P = 0.002) in the patients group. Thus, the presence of chronic inflammation in HD patients may raise serum ferritin unrelated to iron stores, and reduce its diagnostic value.