Abstract
Lung squamous cell carcinoma (LUSC), representing approximately 25% of all lung cancer cases, is the second most prevalent histological subtype. While Family with sequence similarity 83 member A (FAM83A) is recognized as an oncogene across various tumors, its prognostic impact and biological roles specifically in LUSC have yet to be comprehensively elucidated. Our investigation explored the expression variability of the FAM83A gene and its implications for both patient prognosis and immune system modulation, utilizing data sourced from TCGA and the GEO. The scope of this analysis encompassed cohorts comprising 509 patients internally and 225 patients externally, specifically aimed at determining the prognostic significance of FAM83A expression. For methodological rigor, the larger internal cohort was systematically divided, with 60% forming a training set and the remaining 40% constituting a validation set, all assigned randomly. Through multivariate analysis that included clinicopathological factors and FAM83A expression assessed via immunohistochemistry (IHC), we identified key predictors for developing a novel LUSC prognostic model. Both internal and external validation sets utilized ROC curves, calibration curves, and DCA to evaluate the model's precision and clinical applicability. High levels of FAM83A mRNA expression in tumor tissues were linked to unfavourable outcomes for LUSC patients in both the TCGA and GEO datasets. Detailed analyses indicated that this upregulation of FAM83A mRNA is associated with increased immune cell infiltration and higher levels of immune regulatory gene expression. Retrospective analyses of patient samples further validated the relationship between elevated FAM83A protein expression and poorer prognoses. From these multivariate analysis results, we formulated a prognostic model incorporating four independent risk factors: elevated FAM83A expression, male gender, advanced disease stage, and poor differentiation. This model demonstrated strong predictive accuracy, confirmed by ROC and calibration curves, and DCA highlighted its substantial clinical relevance. FAM83A has been validated as a biomarker for forecasting outcomes in LUSC patients, leading to the development of predictive models based on this marker. Furthermore, FAM83A likely contributes to immunomodulatory processes within LUSC tissues.