Abstract

Lung cancer is the leading cause of cancer-related death worldwide, and the most common histologic subtype is lung adenocarcinoma (LUAD). Due to the significant mortality and morbidity rates among patients with LUAD, the identification of novel biomarkers to guide diagnosis, prognosis, and therapy is urgent. Guanosine triphosphate-binding protein 4 (GTPBP4) has been found to be associated with tumorigenesis in recent years, but the underlying molecular mechanism remains to be elucidated. In the present study, we demonstrate that GTPBP4 is significantly overexpressed in LUAD primary tumors. A total of 55 genes were identified as potential targets of GTPBP4. GO enrichment analysis identified the top 25 pathways among these target genes, among which, ribosome biogenesis was shown to be the most central. Each target gene demonstrated strong and complex interactions with other genes. Of the potential target genes, 12 abnormally expressed candidates were associated with survival probability and correlated with GTPBP4 expression. These findings suggest that GTPBP4 is associated with LUAD progression. Finally, we highlight the importance of the role of GTPBP4 in LUAD in vitro. GTPBP4 knockdown in LUAD cells inhibited proliferation and metastasis, promoted apoptosis, and enhanced sensitivity to TP. Overall, we conclude that GTPBP4 may be considered as a potential biomarker of LUAD.

Highlights

  • Adenocarcinoma is the most prevalent subtype of lung cancer, comprising ~40% of all lung cancer cases [1, 2]

  • Guanosine triphosphate-binding protein 4 (GTPBP4) expression was increased in most human cancer types when compared with adjacent normal tissues (Figure 1(a)), and this difference was significant in lung adenocarcinoma (LUAD) primary tumor tissues (Figure 1(b))

  • GTPBP4 expression profiles in LUAD tissues were compared for gender, node metastasis status (N0, N1, N2, and N3), ethnicity (Caucasian, African-American, and Asian), and stage (S1, S2, S3, and S4)

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Summary

Introduction

Adenocarcinoma is the most prevalent subtype of lung cancer, comprising ~40% of all lung cancer cases [1, 2]. Despite a wealth of research, lung adenocarcinoma (LUAD) remains as a highly aggressive and fatal disease, with an overall survival time of

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