Construction and clinical significance of prognostic risk markers based on cancer driver genes in lung adenocarcinoma

被引:0
作者
Su, Yazhou [1 ]
Huo, Tingting [2 ]
Wang, Yanan [2 ]
Li, Jingyan [2 ]
机构
[1] Xinxiang Med Univ, Affiliated Hosp 1, Dept Thorac Surg, 88 Jiankang Rd, Weihui 453100, Henan, Peoples R China
[2] Xinxiang Med Univ, Affiliated Hosp 1, Dept Oncol, Weihui 453100, Henan, Peoples R China
关键词
Lung adenocarcinoma; Cancer driver genes; Biomarkers; Tumor microenvironment; Mutation landscape; Drug sensitivity; CELLS; KLF4; PROLIFERATION; AMPLIFICATION; LOCALIZATION; EXPRESSION; RESISTANCE; MUTATIONS; CARCINOMA; CISPLATIN;
D O I
10.1007/s12094-024-03703-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Cancer driver genes (CDGs) have been reported as key factors influencing the progression of lung adenocarcinoma (LUAD). However, the role of CDGs in LUAD prognosis has not been fully elucidated. Methods LUAD transcriptome data and CDG-related data were obtained from public databases and literature. Differentially expressed CDGs (DE-CDGs) greatly associated with LUAD survival (P < 0.05) were identified to establish a prognostic model. In addition, immune analysis of high-risk (HR) and low-risk (LR) groups was conducted by utilizing the CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms to assess immune differences. Subsequently, mutation analysis was conducted using maftools. Finally, candidate drugs were identified using the CellMiner database. Results 40 DE-CDGs significantly associated with LUAD survival and 11 DE-CDGs associated with prognosis were identified through screening. Regression analysis revealed that risk score can independently predict LUAD prognosis (P < 0.05). Immune landscape analysis revealed that compared to the HR group, the LR group had higher immune scores and high infiltration of various immune cells such as follicular helper B cells and T cells. Mutation landscape analysis demonstrated that missense mutation was the most common mutation type in both risk groups. Drug prediction analysis revealed strong correlations of fulvestrant, S-63845, sapacitabine, lomustine, BLU-667, SR16157, motesanib, AZD-9496, XK-469, dimethylfasudil, P-529, and imatinib with the model genes, suggesting their potential as candidate drugs targeting the model genes. Conclusion This study identified 11 effective biomarkers, DE-CDGs, which can predict LUAD prognosis and explored the biological significance of CDGs in LUAD prognosis, immunotherapy, and treatment.
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收藏
页码:1539 / 1557
页数:19
相关论文
共 62 条
[1]   Diagnosis of lung cancer by flexible fiberoptic bronchoscopy: a descriptive study [J].
Biciusca, Viorel ;
Popescu, Iulian Alin Silviu ;
Trasca, Diana Maria ;
Olteanu, Mihai ;
Stan, Ionelia Sorina ;
Durand, Patricia ;
Camen, Georgiana-Cristiana ;
Balteanu, Mara Amalia ;
Cazacu, Irina Mihaela ;
Demetrian, Alin Dragos ;
Streba, Costin Teodor ;
Calarasu, Cristina ;
Cioboata, Ramona .
ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY, 2022, 63 (02) :369-381
[2]   Activating HER2 Mutations in HER2 Gene Amplification Negative Breast Cancer [J].
Bose, Ron ;
Kavuri, Shyam M. ;
Searleman, Adam C. ;
Shen, Wei ;
Shen, Dong ;
Koboldt, Daniel C. ;
Monsey, John ;
Goel, Nicholas ;
Aronson, Adam B. ;
Li, Shunqiang ;
Ma, Cynthia X. ;
Ding, Li ;
Mardis, Elaine R. ;
Ellis, Matthew J. .
CANCER DISCOVERY, 2013, 3 (02) :224-237
[3]   Driven by by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer [J].
Castellanos, Emily ;
Feld, Emily ;
Horn, Leora .
JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (04) :612-623
[4]   Somatic selection distinguishes oncogenes and tumor suppressor genes [J].
Chandrashekar, Pramod ;
Ahmadinejad, Navid ;
Wang, Junwen ;
Sekulic, Aleksandar ;
Egan, Jan B. ;
Asmann, Yan W. ;
Kumar, Sudhir ;
Maley, Carlo ;
Liu, Li .
BIOINFORMATICS, 2020, 36 (06) :1712-1717
[5]   The predictive prognostic values of CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 in lung cancer [J].
Chen, Yuhao ;
Shen, Lu ;
Chen, Bairong ;
Han, Xiao ;
Yu, Yunchi ;
Yuan, Xiaosa ;
Zhong, Lou .
ANNALS OF TRANSLATIONAL MEDICINE, 2021, 9 (10)
[6]   Frequent overexpression of the genes FXR1, CLAPM1 and E1F4G located on amplicon 3q26-27 in squamous cell carcinoma of the lung [J].
Comtesse, Nicole ;
Keller, Andreas ;
Diesinger, Isabel ;
Bauer, Christine ;
Kayser, Klaus ;
Huwer, Hanno ;
Lenhof, Hans-Peter ;
Meese, Eckart .
INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (12) :2538-2544
[7]   Annual report to the nation on the status of cancer, part 1: National cancer statistics [J].
Cronin, Kathleen A. ;
Scott, Susan ;
Firth, Albert U. ;
Sung, Hyuna ;
Henley, S. Jane ;
Sherman, Recinda L. ;
Siegel, Rebecca L. ;
Anderson, Robert N. ;
Kohler, Betsy A. ;
Benard, Vicki B. ;
Negoita, Serban ;
Wiggins, Charles ;
Cance, William G. ;
Jemal, Ahmedin .
CANCER, 2022, 128 (24) :4251-4284
[8]  
Cui C., 2021, CELL, V184, pe13
[9]  
Cui XX, 2020, INT J CLIN EXP PATHO, V13, P944
[10]   Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations [J].
Dantoing, Edouard ;
Piton, Nicolas ;
Salaun, Mathieu ;
Thiberville, Luc ;
Guisier, Florian .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (12)