Suspected Molecular Links in Sebaceous Gland Carcinoma of the Eyelid: A scoping review

Abstract

Objectives This review aimed to conduct a comprehensive analysis of mismatch gene defect, cell cycle dysregulation, and anomalous signaling—including Wnt/β-catenin, hedgehog, and caspase-3/YAP signaling—in relation to the phenotypic presentation of eyelid sebaceous gland carcinoma (SGC) patients. This review also includes in-silico analysis to explore selectively expressed proteins (SEPs) through network-based analysis. Methods A thoroughly literature search was performed using PubMed, Google scholar, and Web of Science databases to provide updated knowledge on critical genes and related signaling pathways in SGC pathogenesis by using specific and relevant terms. A protein-protein interaction (PPI) network was constructed for selected genes with strong evidence from the literature, using STRING 11.0 database and Cytoscape 3.7.1 software. Results This review highlights crucial genes and proteins involved in the progression of eyelid SGC. Mismatch repair (MMR) genes are integral to SGC in patients, essential for maintaining genomic integrity. This review also describes mutational analysis, noting that mutations primarily occur in MLH1 and MSH2, followed by MSH6, PMS2 and p53. In patients with SGC, mutations or dysregulation of factors or genes involved in hedgehog, β-catenin, caspase-3/YAP, and C-MYC-AR-p53 signaling are crucial during tumorigenesis. The network-based approach elucidates the roles of essential genes, including MMR genes, and experimentally determines interactions, co-expression, and combined scores. The lowest combined scores were observed for CTNNB1 and SHH. Additionally, the role of immune checkpoint regulators—including PD-1, PD-L1, and CTLA—is investigated, revealing that their dysregulation leads to poor cancer cell presentation to immune cells. Conclusion We summarize the literature on crucial genes (e.g., MMR genes) and related signaling pathways (e.g., Wnt/β-catenin, hedgehog, and Capspase-3/YAP signaling) in the pathogenesis of eyelid SGC. Eyelid SGC is an aggressive tumor typically associated with MMR gene defects compared to other critical genes involved in tumorigenesis. In-silico analysis provides a better understanding of critical genes expressed in sebaceous glands and their role in SGC pathogenesis. These differentially expressed genes in tumor cells could improve SGC diagnosis and serve as potential targets for drug therapy.