Identification and validation of a disulfidptosis-related genes prognostic signature in lung adenocarcinoma
Yanpeng Zhang,
Jingyang Sun,
Meng Li,
Liren Hou,
Zhiyu Wang,
Huanhuan Dong,
Wenjun Xu,
Rongxuan Jiang,
Yuhan Geng,
Chungen Guan,
Zijiang Zhu,
Hongyi Wang,
Qiuyu Gong,
Guangjian Zhang
Affiliations
Yanpeng Zhang
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Jingyang Sun
The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China; Department of Thoracic Surgery, Gansu Central Hospital, Lanzhou, China
Meng Li
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
Liren Hou
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Zhiyu Wang
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Huanhuan Dong
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Wenjun Xu
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Rongxuan Jiang
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
Yuhan Geng
Department of Thoracic Surgery, Gansu Central Hospital, Lanzhou, China
Chungen Guan
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Thoracic Surgery, Gansu Central Hospital, Lanzhou, China
Zijiang Zhu
Department of Thoracic Surgery, Gansu Central Hospital, Lanzhou, China
Hongyi Wang
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Corresponding author.
Qiuyu Gong
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Corresponding author.
Guangjian Zhang
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Corresponding author.
Disulfidptosis, a newly revealed form of cell death, regulated by numerous genes that has been recently identified. The exact role of disulfidptosis in lung adenocarcinoma (LUAD) still uncertain. Objective of this study was to explore potential prognostic markers among disulfidptosis genes in LUAD. By combining transcriptomic information from Gene Expression Omnibus databases and The Cancer Genome Atlas, we identified differentially expressed and prognostic disulfidptosis genes. By conducting least absolute shrinkage and selection operator with multivariate Cox regression, four disulfidptosis genes were selected to create the prognostic signature. The implementation of the signature separated the training and validation cohorts into groups with high- and low-risk. Subsequently, the model was verified by conducting an independent analysis of receiver operating characteristic (ROC) curves. Further comparisons were made between the two risk-divided groups with regards the tumor microenvironment, immune cell infiltration, immunotherapy response, and drug sensitivity. The signature was constructed using four disulfidptosis-related genes: SLC7A11, SLC3A2, NCKAP1, and GYS1. According to ROC curves, the signature was effective for predicting LUAD prognosis. In addition, the prognostic signature correlated with sensitivity to chemotherapeutic agents and the efficacy of immunotherapy in LUAD. Finally, through external validation, we showed that NCKAP1 are correlated with tumor migration, proliferation, and invasion of LUAD cells. GYS1 affects immune cell, especially M2 macrophage infiltration in the tumor microenvironment. The disulfidptosis four-gene model can reliably predict the prognosis of patients diagnosed with LUAD, thereby providing valuable information for clinical applications and immunotherapy.
