HILPDA: A Novel Prognostic Biomarker for Lung Adenocarcinoma Identified by Integrated Bioinformatic Analysis and Experimental Validation

Background Lung adenocarcinoma (LUAD) represents the most prevalent pathological subtype of non-small cell lung cancer (NSCLC), a malignancy that accounts for 80–85% of all lung cancer cases. However, the expression profile of HILPDA and its functional significance in LUAD remain largely elusive. In this study, we sought to elucidate the regulatory mechanism of HILPDA in LUAD progression through integrated bioinformatics analyses, with the aim of providing novel insights to inform the clinical management of this disease. Methods We analyzed the expression level of HILPDA and its correlation with clinical characteristics using data from the The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. Kaplan-Meier (K-M) survival curves were generated to assess overall survival (OS) and disease-free survival (DFS). Univariate Cox regression was performed incorporating all clinicopathological parameters and HILPDA expression; factors with P  < 0.05 were further included in multivariate Cox regression to evaluate whether HILPDA could serve as an independent prognostic factor for LUAD. Additionally, Gene Set Enrichment Analysis (GSEA) was conducted. Immune cell infiltration patterns were characterized primarily via ESTIMATE and CIBERSORT algorithms. Furthermore, regulatory gene prediction and competing endogenous RNA (ceRNA) network construction were carried out. Finally, qRT-PCR was employed to validate the bioinformatics findings in clinical samples and cell lines. Western blotting (WB) was used to quantify HILPDA protein expression after gene knockdown, while CCK-8, Transwell chamber, and scratch assays were performed to detect cell proliferation, invasion, and migration, respectively. Results Bioinformatics analyses revealed that HILPDA expression was significantly higher in LUAD tissues than in adjacent non-tumor tissues, and correlated closely with multiple clinical characteristics. LUAD patients with high HILPDA expression exhibited shorter overall survival (OS) and disease-free survival (DFS) compared to those with low expression. Univariate and multivariate Cox regression analyses confirmed that HILPDA could serve as an independent prognostic factor for LUAD. Enrichment analysis results indicated that HILPDA participates in a variety of critical regulatory pathways and molecular processes, and its expression was significantly associated with immune cell infiltration patterns. Furthermore, clinical samples and LUAD cell lines showed higher relative HILPDA expression than corresponding controls, and HILPDA knockdown was found to inhibit the proliferation, invasion, and migration of LUAD cells. Conclusions HILPDA was significantly upregulated in LUAD tissues and cell lines compared with adjacent non-tumor counterparts, and its expression correlated with clinical characteristics as well as patient survival and prognosis. Moreover, HILPDA knockdown inhibited the proliferation, invasion, and migration of LUAD cells, supporting its role as an independent prognostic factor for LUAD.