2. Academic Validation
  3. Screening and Validation of Significant Genes with Poor Prognosis in Pathologic Stage-I Lung Adenocarcinoma

Screening and Validation of Significant Genes with Poor Prognosis in Pathologic Stage-I Lung Adenocarcinoma

  • J Oncol. 2022 Apr 11;2022:3794021. doi: 10.1155/2022/3794021.
Yujie Deng  # 1 2 3,  Xiaohui Chen  # 4 5,  Chuanzhong Huang 6,  Jun Song 1 2,  Sisi Feng 1 2,  Xuzheng Chen 1 2,  Ruixiang Zhou 1 2
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, Fujian, China.
  • 2 Key Laboratory of Gastrointestinal Cancer, Ministry of Education, Fujian Medical University, Fuzhou 350108, Fujian, China.
  • 3 Molecular Oncology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, China.
  • 4 Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian Province 350014, China.
  • 5 College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, China.
  • 6 Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China.
  • # Contributed equally.
PMID: 35444699 DOI: 10.1155/2022/3794021
Abstract

Background: Although more pathologic stage-I lung adenocarcinoma (LUAD) was diagnosed recently, some relapsed or distantly metastasized shortly after radical resection. The study aimed to identify biomarkers predicting prognosis in the pathologic stage-I LUAD and improve the understanding of the mechanisms involved in tumorigenesis.

Methods: We obtained the expression profiling data for non-small cell lung Cancer (NSCLC) patients from the NCBI-GEO database. Differentially expressed genes (DEGs) between early-stage NSCLC and normal lung tissue were determined. After function enrichment analyses on DEGs, the protein-protein interaction (PPI) network was built and analyzed with the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Overall survival (OS) and mRNA levels of genes were performed with Kaplan-Meier analysis and Gene Expression Profiling Interactive Analysis (GEPIA). qPCR and western blot analysis of hub genes in stage-I LUAD patients validated the significant genes with poor prognosis.

Results: A total of 172 DEGs were identified, which were mainly enriched in terms related to management of extracellular matrix (ECM), receptor signaling pathway, cell adhesion, activity of endopeptidase, and receptor. The PPI network identified 11 upregulated hub genes that were significantly associated with OS in NSCLC and highly expressed in NSCLC tissues compared with normal tissues by GEPIA. Elevated expression of ANLN, EXO1, KIAA0101, RRM2, TOP2A, and UBE2T were identified as potential risk factors in pathologic stage-I LUAD. Except for ANLN and KIAA0101, the hub genes mRNA levels were higher in tumors compared with adjacent non-cancerous samples in the qPCR analysis. The hub genes protein levels were also overexpressed in tumors. In vitro experiments showed that knockdown of UBE2T in LUAD cell lines could inhibit cell proliferation and cycle progression.

Conclusions: The DEGs can probably be used as potential predictors for stage-I LUAD worse prognosis and UBE2T may be a potential tumor promoter and target for treatment.

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