AP5S1 is a Promising Prognostic and Predictive Biomarker Associated with Tumor Stemness in Lung Squamous Cell Carcinoma

Abstract

Background: Lung squamous cell carcinoma (LUSC) is considered the second most prevalent subtype of non-small cell lung cancer (NSCLC), with a high frequency of somatic mutations and limited therapeutic options. Adaptor-associated protein complex 5 subunit sigma 1 (AP5S1) is a component of fifth adaptor proteins complexes. However, the correlation between AP5S1 expression and the occurrence, development, and tumor stemness in LUSC has rarely been studied. Therefore, this study aimed to elucidate the correlation between AP5S1 expression and the stemness of LUSC. Methods: The transcriptomic and functional clinic data of LUSC were accessed from various publicly accessible databases. The data were intensively analyzed using various bioinformatics tools and visualized employing statistical packages. Subsequently, the expression levels were validated through quantitative real-time polymerase chain reaction (qRT-PCR) using LUSC cell lines. The correlations between AP5S1 expression and prognosis, potential pathogenic mechanisms, tumor stemness, immune cell infiltration, DNA methylation, drug sensitivity, and malignant biological behavior in LUSC patients were assessed utilizing both bioinformatics approaches and various assays such as Cell Counting Kit-8 (CCK-8), colony formation, tumor sphere formation, and Transwell assays. Results: This study indicated a significant oncogenic role of AP5S1 in LUSC. Moreover, AP5S1 was confirmed as an independent prognostic risk factor for LUSC. Additionally, there was a strong association between AP5S1 expression and cancer stemness, immunity, DNA methylation, and drug treatment response. Furthermore, the knocking down of AP5S1 inhibited cell proliferation, migration, invasion, and stemness in LUSC in vitro. Conclusions: AP5S1 could be a promising prognostic indicator and a potential therapeutic target closely related to tumor stemness in LUSC patients.