Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies, characterized by complex molecular alterations that drive its progression. Understanding the molecular mechanisms underlying UCEC is crucial for developing effective diagnostic, prognostic, and therapeutic strategies. Immune-related genes, such as COL1A1, ITGB1, THY1, and PDGFRA, have been implicated in various cancers, but their roles in UCEC remain underexplored. In this study, we investigate the roles of these genes in the development and progression of UCEC. Using both in silico and in vitro approaches, we found that these genes were dysregulated in UCEC. Our results revealed the downregulation of COL1A1, ITGB1, THY1, and PDGFRA in UCEC compared to normal tissues. Further, promoter methylation analysis showed increased methylation of these genes in UCEC. Survival analysis highlighted their potential as prognostic markers, with lower expression linked to poor patient survival. Additionally, genetic alteration analysis demonstrated mutations in these genes across UCEC patients. Our results also showed that overexpression of COL1A1 in KLE and HEC-1B cells significantly reduced cell proliferation, colony formation, and migration, indicating that COL1A1 overexpression impacts critical cellular behaviors in UCEC. Finally, we explored the therapeutic potential of targeting these genes, suggesting that they may offer valuable insights for personalized treatment strategies in UCEC. This study identifies COL1A1, ITGB1, THY1, and PDGFRA as crucial regulators of UCEC progression, with altered expression linked to tumor behavior and patient survival. Overexpression of COL1A1 impaired cell proliferation, colony formation, and migration. Future research should focus on elucidating the molecular mechanisms of these genes, exploring their therapeutic targeting in preclinical models, and validating their clinical potential as biomarkers in larger patient cohorts to improve treatment strategies for UCEC.