Research Paper Volume 16, Issue 5 pp 4378—4395
The prognosis, chemotherapy and immunotherapy efficacy of the SUMOylation pathway signature and the role of UBA2 in lung adenocarcinoma
- 1 Central Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China
- 2 Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China
- 3 Jiangxi Health Commission Key Laboratory of Leukemia, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi 341000, China
- 4 Laboratory Animal Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, China
- 5 900 Hospital of The Joint Logistics Team, Fuzhou, Fujian 350001, China
- 6 Department of Pulmonary and Critical Care Medicine, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian 350001, China
- 7 Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361000, China
- 8 Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350001, China
Received: October 18, 2023 Accepted: January 23, 2024 Published: February 23, 2024
https://doi.org/10.18632/aging.205594How to Cite
Copyright: © 2024 Yu 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
Lung adenocarcinoma (LUAD) is one of the most common malignant tumors worldwide. Small Ubiquitin-like Modifier (SUMO)-ylation plays a crucial role in tumorigenesis. However, the SUMOylation pathway landscape and its clinical implications in LUAD remain unclear. Here, we analyzed genes involved in the SUMOylation pathway in LUAD and constructed a SUMOylation pathway signature (SUMOPS) using the LASSO-Cox regression model, validated in independent cohorts. Our analysis revealed significant dysregulation of SUMOylation-related genes in LUAD, comprising of favorable or unfavorable prognostic factors. The SUMOPS model was associated with established molecular and histological subtypes of LUAD, highlighting its clinical relevance. The SUMOPS stratified LUAD patients into SUMOPS-high and SUMOPS-low subtypes with distinct survival outcomes and adjuvant chemotherapy responses. The SUMOPS-low subtype showed favorable responses to adjuvant chemotherapy. The correlations between SUMOPS scores and immune cell infiltration suggested that patients with the SUMOPS-high subtype exhibited favorable immune profiles for immune checkpoint inhibitor (ICI) treatment. Additionally, we identified UBA2 as a key SUMOylation-related gene with an increased expression and a poor prognosis in LUAD. Cell function experiment confirmed the role of UBA2 in promoting LUAD cell proliferation, invasion, and migration. These findings provide valuable insights into the SUMOylation pathway and its prognostic implications in LUAD, paving the way for personalized treatment strategies and the development of novel therapeutic targets.
Abbreviations
LUAD: Lung adenocarcinoma; SUMO: Small Ubiquitin-like Modifier; SUMOPS: SUMOylation pathway signature; ICI: Immune checkpoint inhibitor; SCLC: Small cell lung cancer; NSCLC: Non-small cell lung cancer; LUSC: Lung squamous cell carcinoma; Ubc9: Ubiquitin-conjugating enzyme 9; GSVA: Gene set variation analysis; TRIM28: Tripartite motif-containing 28; RANGAP1: Ran GTPase-activating protein 1; SAE1: SUMO-activating enzyme subunit 1; UBA2: Ubiquitin-like modifier-activating enzyme 2; RELA: v-rel avian reticuloendotheliosis viral oncogene homolog A; SLF1: SMC5-SMC6 Complex Localization Factor 1; TRIM38: Tripartite motif-containing 38; CAPN3: Calpain 3; PWDD3: Peptidylprolyl isomerase domain and WD repeat-containing protein 3; TRIM27: Tripartite motif-containing 27; EGR2: Early growth response 2; RNF212B: Ring finger protein 212B; TP53: Tumor Protein p53; TTN: Titin; CSMD3: CUB And Sushi Multiple Domains 3; MUC16: Mucin 16, Cell Surface Associated; RYR2: Ryanodine Receptor 2; USH2A: Usherin; LRP1B: LDL Receptor Related Protein 1B; FLG: Filaggrin; KRAS: Kirsten Rat Sarcoma Viral Oncogene Homolog; ZFHX4: Zinc Finger Homeobox 4; SPTA1: Spectrin Alpha, Erythrocytic 1; NAV3: Neuron Navigator 3; PCLO: Piccolo Presynaptic Cytomatrix Protein; XIRP2: Xin Actin Binding Repeat Containing 2; ZNF536: Zinc Finger Protein 536; CSMD1: CUB And Sushi Multiple Domains 1; ANK2: Ankyrin 2; KEAP1: Kelch Like ECH Associated Protein 1; APOB: Apolipoprotein B; COL11A1: Collagen Type XI Alpha 1 Chain; MUC17: Mucin 17, Cell Surface Associated; FAT3: FAT Atypical Cadherin 3; ADAMTS12: A Disintegrin And Metalloproteinase With Thrombospondin Motifs 12; PCDH15: Protocadherin Related 15; RAS/MAPK: Rat Sarcoma/Mitogen-Activated Protein Kinase; ER: Estrogen Receptor; OS: Overall Survival; TIDE: Tumor Immune Dysfunction and Exclusion.