Research Paper Volume 16, Issue 3 pp 2320—2339
Comprehensive analysis of ALG3 in pan-cancer and validation of ALG3 as an onco-immunological biomarker in breast cancer
- 1 Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
- 2 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
- 3 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
- 4 Basic Medical Academy, Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Received: September 18, 2023 Accepted: December 14, 2023 Published: February 7, 2024
https://doi.org/10.18632/aging.205483How to Cite
Copyright: © 2024 Xue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
ALG3 has significant modulatory function in the process of tumor development. Yet how ALG3 involves in the advancement of different malignancies isn’t fully understood. We performed a pan-cancer assessment on ALG3 utilizing datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to examine its tumor-related roles across malignancies and its link to particular molecules and cells in the tumor microenvironment (TME). Furthermore, we focused on breast cancer to examine the influence of ALG3-mediated signaling pathways and intercellular interactions in the advancement of tumors. The biological effects of ALG3 were verified by breast cancer cells. Enhanced ALG3 expression was discovered to be substantially linked to patients' grim prognoses in a number of malignancies. Furthermore, the expression of ALG3 in the TME was linked to the infiltration of stromal and immune cells, and ALG3-related immune checkpoints, TMB, and MSI were also discovered. We also discovered that cancer patients having a high level of ALG3 exhibited a lower probability of benefiting from immunotherapy. Furthermore, our research found that KEGG enrichment, single-cell RNA and spatial sequencing analyses were effective in identifying key signaling pathways in ALG3-associated tumor growth. In vitro, knockdown of ALG3 could decrease the proliferation of breast cancer cells. In summary, our research offers a comprehensive insight into the advancement of tumors under the mediation of ALG3. ALG3 appears to be intimately associated with tumor development in the TME. ALG3 might be a viable treatment target for cancer therapy, particularly in the case of breast cancer.
Abbreviations
ALG3: alpha-1,3-mannosyltransferase; TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression; TME: tumor microenvironment; MSI: microsatellite instability; TMB: tumor mutation burden; OS: overall survival; DFS: disease-free survival; ICB: immune checkpoint blockade; AUC: area under the curve; RNAss: RNA stemness score; DNAss: DNA stemness score; TIL: tumor-infiltrating lymphocytes; CSCs: cancer stem cells; FBS: fetal bovine serum; CCLE: Cancer Cell Line Encyclopedia; ESTIMATE: Estimation of stromal and Immune cells in Malignant Tumor tissues using the Expression data; TIMER: Tumor Immune Estimation Resource; TISCH: Tumor Immune Single-cell Hub; HPA: The Human Protein Atlas; IHC: immunohistochemical; ROC: receiver operating characteristic.