Construction and validation of an EGFR-related risk signature identified SHC1 as a prognostic biomarker for lung adenocarcinoma.

Abstract

Background: Lung adenocarcinoma (LUAD) is a significant subtype of lung cancer, contributing to high mortality rates and posing substantial challenges to public health. This study aims to explore the significance of the epidermal growth factor receptor (EGFR)-related gene SHC1 in the progression and prognosis of LUAD.

Methods: Patient RNA sequencing (RNA-seq) and clinical data were acquired from The Cancer Genome Atlas (TCGA) database. Using the least absolute shrinkage and selection operator (LASSO) Cox regression, we then generated a multigene signature of EGFR signaling-related genes (ESRGs) for the prognostic prediction of LUAD. We investigated the relationship between SHC1 gene expression and immune cell infiltration by employing single-sample gene set enrichment analysis (ssGSEA). The potential functional role of the SHC1 gene was evaluated through GSEA. Additionally, the association between SHC1 expression and clinical data was investigated. Immunohistochemistry was utilized to assess SHC1 expression in 88 cases of invasive pulmonary adenocarcinoma.

Results: Univariate Cox regression analysis identified that increased expression of SHC1 correlated with poorer overall survival (OS). SHC1 exhibited significantly elevated expression levels in LUAD tissues. Moreover, elevated levels of SHC1 gene expression correlated strongly with advanced tumor (T), node (N), and metastasis (M) stages and were significantly associated with immune cell infiltration in LUAD. Furthermore, marked increases in SHC1 protein expression were observed in patients diagnosed with invasive pulmonary adenocarcinoma.

Conclusions: These findings suggest that SHC1 plays a crucial oncogenic role in LUAD. Increased SHC1 expression in LUAD was associated with disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration.