Objective: To identify the key genes related to the occurrence and development of lung adenocarcinoma by bioinformatics, and to explore its potential application value in the survival and prognosis of lung adenocarcinoma. Methods: The transcriptome data from the cancer genome atlas (TCGA) database were screened for differentially expressed genes between lung adenocarcinoma and normal tissues via R software. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were subsequently performed to study the function and pathway enrichment of the identified DEGs. Weighted gene co-expression network analysis (WGCNA) was used to identify the key modules and the genes in key modules based on the lung adenocarcinoma dataset from TCGA database. Kaplan-Meier analysis and Cox proportional hazards regression model were used to analyze the predictors related to the prognosis of patients with lung adenocarcinoma. Results: A total of 1 749 DEGs based on the gene expression data from TCGA were screened. By WGCNA, there were six gene modules related to the clinical characteristics of patients with lung adenocarcinoma, of which the blue, brown, turquoise, yellow and green modules showed the highest positive correlation with the occurrence and development of lung adenocarcinoma (r=0.69, r=0.42, r=-0.65, r=-0.41, r=-0.30, P＜0.01). Ultimately, CDK1, DLGAP5 and PLK1 were identified by integrating the DEGs with key module genes of WGCNA and then the overexpression of CDK1, DLGAP5 and PLK1 was associated with a poor prognosis in patients with lung adenocarcinoma (P＜0.05). Conclusion: CDK1, DLGAP5 and PLK1 are associated with a poor prognosis of lung adenocarcinoma, which as potential therapeutic targets for improving the prognosis of lung adenocarcinoma.
JIANG Lixin
,
ZHANG Yumeng
. Analysis of hub genes associated with lung adenocarcinoma prognosis based on WGCNA[J]. Journal of Baotou Medical College, 2025
, 41(10)
: 34
-40
.
DOI: 10.16833/j.cnki.jbmc.2025.10.007
[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263.
[2] Chen Z, Fillmore CM, Hammerman PS, et al. Non-small-cell lung cancers: a heterogeneous set of diseases[J]. Nat Rev Cancer, 2014, 14(8): 535-546.
[3] 何海斌, 马佳宏, 唐妍, 等. 肺腺癌分型方法及临床应用的研究进展[J]. 生命科学研究, 2024: 1-10.
[4] Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer[J]. Nat Rev Mol Cell Biol, 2022, 23(1): 74-88.
[5] Mughal MJ, Bhadresha K, Kwok HF. CDK inhibitors from past to present: a new wave of cancer therapy[J]. Semin Cancer Biol, 2023, 88: 106-122.
[6] Guan T, Li M, Song Y, et al. Phosphorylation of USP29 by CDK1 governs TWIST1 stability and oncogenic functions[J]. Adv Sci (Weinh), 2023, 10(11): e2205873.
[7] Zeng K, Li W, Wang Y, et al. Inhibition of CDK1 overcomes oxaliplatin resistance by regulating ACSL4-mediated ferroptosis in colorectal cancer[J]. Adv Sci (Weinh), 2023, 10(25): e2301088.
[8] Subramaniam D, Periyasamy G, Ponnurangam S, et al. CDK-4 inhibitor P276 sensitizes pancreatic cancer cells to gemcitabine-induced apoptosis[J]. Mol Cancer Ther, 2012, 11(7): 1598-1608.
[9] Wu CX, Wang XQ, Chok SH, et al. Blocking CDK1/PDK1/β-Catenin signaling by CDK1 inhibitor RO3306 increased the efficacy of sorafenib treatment by targeting cancer stem cells in a preclinical model of hepatocellular carcinoma[J]. Theranostics, 2018, 8(14): 3737-3750.
[10] Tong J, Yang H, Eom SH, et al. Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus[J]. Biochem Biophys Res Commun, 2014, 452(1): 130-135.
[11] Zhang H, Liu Y, Tang S, et al. Knockdown of DLGAP5 suppresses cell proliferation, induces G2/M phase arrest and apoptosis in ovarian cancer[J]. Exp Ther Med, 2021, 22(5): 1245.
[12] Chen M, Zhang S, Wang F, et al. DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target[J]. J Transl Med, 2024, 22(1): 20.
[13] Tang X, Zhou H, Liu Y. High expression of DLGAP5 indicates poor prognosis and immunotherapy in lung adenocarcinoma and promotes proliferation through regulation of the cell cycle[J]. Dis Markers, 2023, 2023: 9292536.
[14] Zitouni S, Nabais C, Jana SC, et al. Polo-like kinases:structural variations lead to multiple functions[J]. Nat Rev Mol Cell Biol, 2014, 15(7): 433-452.
[15] Gao P, Hao JL, Xie QW, et al. PELO facilitates PLK1-induced the ubiquitination and degradation of Smad4 and promotes the progression of prostate cancer[J]. Oncogene, 2022, 41(21): 2945-2957.
[16] Lin P, Xiong DD, Dang YW, et al. The anticipating value of PLK1 for diagnosis, progress and prognosis and its prospective mechanism in gastric cancer: a comprehensive investigation based on high-throughput data and immunohistochemical validation[J]. Oncotarget, 2017, 8(54): 92497-92521.
[17] Kong Y, Allison DB, Zhang Q, et al. The kinase PLK1 promotes the development of Kras/Tp53-mutant lung adenocarcinoma through transcriptional activation of the receptor RET[J]. Sci Signal, 2022, 15(754): eabj4009.
[18] Chan KK, Wong OG, Wong ES, et al. Impact of iASPP on chemoresistance through PLK1 and autophagy in ovarian clear cell carcinoma[J]. Int J Cancer, 2018, 143(6): 1456-1469.
[19] Smith L, Farzan R, Ali S, et al. The responses of cancer cells to PLK1 inhibitors reveal a novel protective role for p53 in maintaining centrosome separation[J]. Sci Rep, 2017, 7(1): 16115.
[20] Yan W, Yu H, Li W, et al. Plk1 promotes the migration of human lung adenocarcinoma epithelial cells via STAT3 signaling[J]. Oncol Lett, 2018, 16(5): 6801-6807.
