14 | Unraveling the transcriptomic landscape of poorly differentiated cutaneous squamous cell carcinoma: toward prognostic biomarkers
Lorenzo Bellando1, Chiara Anselmo2, Giulia Orlando3, Leonardo Panarelli2, Ilaria Palma2, Virginia Caliendo3, Franco Picciotto4, Gabriele Roccuzzo5, Pietro Quaglino5, Simone Ribero5, Rebecca Senetta3 | 1Pathology Unit, Città Della Salute e Della Scienza University of Turin; 2Department of Medical Sciences, Pathology Unit, University of Turin; 3Department of Oncology, Pathology Unit, University of Turin; 4Department of Surgery, Dermatologic Surgery Section, Azienda Ospedaliera Universitaria Città della Salute e della Scienza of Turin; 5Department of Medical Sciences, Section of Dermatology, University of Turin, Italy.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Background: Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer, with a 10-year survival rate >90% after surgical resection. However, recurrence and nodal/visceral metastasis can significantly affect survival and outcomes. In particular, poorly differentiated (G3) cSCC is associated with a higher risk of recurrence. To date, precise patient risk- prognostication needs to reach in clinical practice. The aim of this study was to understanding the molecular events characterizing G3-cSCC progression.
Methods: From a retrospective series of patients with G3-cSCC diagnosed at the Turin University Hospital (2016-2021) (1), a subgroup of 48 cases were analyzed by performing a transcriptomic analysis using the nCounter® PanCancer Progression Panel (NanoString Technologies, Seattle, WA, USA). Specifically, 16 progressed G3-cSCC (cutaneous/lymph node/visceral progression), 16 G3-cSCC-LR (non-progressed, negative margins, absence of vascular/perineural invasion and desmoplasia, Breslow thickness ≤6 mm, no immunosuppression, and a follow-up >30 months) and 16 G3-cSCC-HR (non-progressed, negative margins, presence of at least one of the aforementioned parameters, follow-up >30 months) were enrolled.
Results: 21 upregulated genes, including COL1A1, COL1A2, COL5A2, COL3A1, SERPINH1, PLAUR, and CCL11 (p<0.05) and 6 downregulated genes, including PROM1 (p<0.05) were identified comparing progressed G3-cSCC with G3-cSCC-LR. Extracellular matrix remodeling, metabolic regulation, hypoxia, inflammatory signaling and angiogenesis were the most differentially involved pathways between the two groups. Otherwise, comparing G3-cSCC-LR and G3-cSCC-HR hypoxia and angiogenesis pathways were observed. In this comparison, 5 upregulated (ARHG, CYBB, SH2B3, GIMAP6, RAC2, p<0.05) and 4 downregulated (GATA4, KDM1A, CHAD, ASPN, p<0.05) genes were revealed. No differentially expressed genes were detected, comparing progressed G3-cSCC and G3-cSCC-HR. However, pathway analysis highlighted differences in hypoxia signaling, angiogenesis, EMT to metastasis and extracellular matrix remodeling.
Conclusions: Our analysis of mRNA provides a comprehensive evaluation of the pathways that promote recurrence and progression in G3-SCC. These observations may represent a starting point in identifying biomarkers useful in the prognostic stratification of this high-risk subgroup of cSCC.
References:
[1] Roccuzzo G, Orlando G, Rumore MR, et al. Predictors of Recurrence and Progression in Poorly Differentiated Cutaneous Squamous Cell Carcinomas: Insights from a Real-Life Experience. Dermatology. 2024;240(2):329-336.
Downloads
Citations
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
