Research Paper Volume 16, Issue 2 pp 1808—1828

Identification of BANF1 as a novel prognostic biomarker in gastric cancer and validation via in-vitro and in-vivo experiments

Yuanmin Xu1, *, , Xu Wang1, *, , Weiwei Yuan2, , Ling Zhang3, , Wei Chen1, , Kongwang Hu1,4, ,

  • 1 Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
  • 2 Department of General Surgery, Anhui Public Health Clinical Center, Hefei 230022, China
  • 3 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230022, China
  • 4 Department of General Surgery, Fuyang Affiliated Hospital of Anhui Medical University, Fuyang 236000, China
* Equal contribution

Received: September 18, 2023       Accepted: December 14, 2023       Published: January 22, 2024      

https://doi.org/10.18632/aging.205461
How to Cite

Copyright: © 2024 Xu 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

Gastric cancer (GC) is a widespread malignancy characterized by a notably high incidence rate and an unfavorable prognosis. We conducted a meticulous analysis of GC high-throughput sequencing data downloaded from the Gene Expression Omnibus (GEO) repository to pinpoint distinctive genes associated with GC. Our investigation successfully identified three signature genes implicated in GC, with a specific focus on the barrier to autointegration factor 1 (BANF1), which exhibits elevated expression across various cancer types, including GC. Bioinformatic analysis has highlighted BANF1 as a prognostic indicator for patients with GC, with direct implications for immune cell infiltration. To gain a more comprehensive understanding of the significance of BANF1 in GC, we performed a series of in vitro experiments to confirm its high expression in GC tissues and cellular components. Intriguingly, the induction of BANF1 knockdown resulted in a marked attenuation of proliferation, migratory capacity, and invasive potential in GC cells. Moreover, our in vivo experiments using nude mouse models revealed a notable impediment in tumor growth following BANF1 knockdown. These insights underscore the feasibility of BANF1 as a novel therapeutic target for GC.

Abbreviations

GC: Gastric cancer; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; BANF1: barrier to autointegration factor 1; DEGs: differentially expressed genes; PCA: principal component analysis; WGCNA: Weighted co-expression network analysis; LASSO: least absolute shrinkage and selection operator; RF: random forest; SVM-RFE: support vector machine-recursive feature elimination; ESTIMATE: Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data; ssGSEA: single sample Gene Set Enrichment Analysis; GS: gene significance; MM: module membership; ROC: Receiver Operating Characteristic; AUC: area under the curve; OS: overall survival; FP: first progression survival; PPS: post progression survival; FC: fold change; scRNA-seq: single cell RNA sequencing; TISCH: Tumor Immune Single-cell Hub; UMAP: uniform manifold approximation and projection; GSEA: gene set enrichment analysis; TME: tumor microenvironment; t-SNE: t-Distributed Stochastic Neighbor Embedding; TPM: transcripts per kilobase million; PMSF: Phenylmethanesulfonyl fluoride; TBST: Tris buffer Saline containing 0.1% Tween 20; DAPI: 4′,6-diamidino-2-phenylindole; ATCC: American Type Culture Collection; RPMI: Roswell Park Memorial Institute; CCK8: cell counting kit-8; SPF: specific pathogen Free; TdT: Terminal Deoxynucleotidyl Transferase; TUNEL: TdT mediated dUTP Nick End Labeling; TIDE: Tumor Immune Dysfunction and Exclusion; CDX: cell line-derived xenograft; cGAS-STING: Cyclic GMP-AMP synthase (cGAS)-stimulator of the interferon genes (STING); WB: western blot.