Identification of ALG3 as a potential prognostic biomarker in lung adenocarcinoma

Yinjiao Yuan; BaoCheng Xie; Dongbo Guo; Caixiang Liu; Guanming Jiang; Guowei Lai; Yu Zhang; Xiarong Hu; Zhiming Wu; Ruinian Zheng; Linxuan Huang

doi:10.1016/j.heliyon.2023.e18065

Identification of ALG3 as a potential prognostic biomarker in lung adenocarcinoma

Heliyon. 2023 Jul 8;9(7):e18065. doi: 10.1016/j.heliyon.2023.e18065. eCollection 2023 Jul.

Authors

Yinjiao Yuan^{1

2}, BaoCheng Xie³, Dongbo Guo⁴, Caixiang Liu², Guanming Jiang², Guowei Lai^{5

6}, Yu Zhang⁷, Xiarong Hu⁵, Zhiming Wu⁵, Ruinian Zheng², Linxuan Huang²

Affiliations

¹ The First School of Chinical Medicine, Southern Medical University, Guangzhou, 510510, China.
² Department of Oncology, Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, 523059, China.
³ Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
⁴ State Key Laboratory of Marine Resource Utilization in South China Sea, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, China.
⁵ Department of General Surgery, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China.
⁶ General Hospital of Third Division, Xinjiang Production and Construction Corps, Tumushuker, China.
⁷ The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Abstract

Background: The abnormal expression of Alpha-1,3-mannosyltransferase (ALG3) has been implicated in tumor promotion. However, the clinical significance of ALG3 in Lung Adenocarcinoma (LUAD) remains poorly understood. Therefore, we aimed to assess the prognostic value of ALG3 and its association with immune infiltrates in LUAD.

Methods: The transcriptional expression profiles of ALG3 were obtained from the Cancer Genome Atlas (TCGA), comparing lung adenocarcinoma tissue with normal tissues. To determine the prognostic significance of AGL3, Kaplan-Meier plotter, and Cox regression analysis were employed. Logistic regression was utilized to analyze the association between ALG3 expression and clinical characteristics. Additionally, a receiver operating characteristic (ROC) curve and a nomogram were constructed. To explore the underlying mechanisms, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA) was conducted. The relationship between AGL3A mRNA expression and immune infiltrates was investigated using the tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB). Furthermore, an in vitro experiment was performed to assess the impact of ALG3 mRNA on lung cancer stemness abilities and examine key signaling pathway proteins.

Results: Our results revealed the ALG3 mRNA and protein expression in patients with LUAD was much higher than that in adjacent normal tissues. High expression of ALG3 was significantly associated with N stage (N0, HR = 1.98, P = 0.002), pathological stage (stage I, HR = 2.09, P = 0.003), and the number of pack years (<40, HR = 2.58, P = 0.001). Kaplan-Meier survival analysis showed that high expression of ALG3 was associated with poor overall survival (P < 0.001), disease-free survival (P < 0.001), and progression-free interval (P = 0.007). Through multivariate analysis, it was determined that elevated ALG3 expression independently impacted overall survival (HR = 1.325, P = 0.04). The Tumor Immune Estimation Resource discovered a link between ALG3 expression and tumor-infiltrating immune cells in LUAD. Additionally, ROC analysis proved that ALG3 is a reliable diagnostic marker for LUAD (AUC:0.923). Functional pathways analysis identified that ALG3 is negatively correlated with FAT4. We performed qRT-PCR to assess that knockdown ALG3 expression significantly upregulated FAT4 expression. Spheroid assay and flow cytometry analysis results showed that downregulated of ALG3 inhibited H1975 cell line stemness. Western blot analysis revealed that decreased ALG3 inhibited the YAP/TAZ signal pathway.

Conclusion: High expression of ALG3 is strongly associated with poor prognosis and immune infiltrates in LUAD.

Keywords: ALG3; Immune infiltration; Lung adenocarcinoma; Prognostic biomarker.