An evaluation of KIF20A as a prognostic factor and therapeutic target for lung adenocarcinoma using integrated bioinformatics analysis

被引:8
作者
Sun, Dongjie [1 ]
Zhang, Haiying [2 ]
Zhang, Chi [3 ]
Wang, Lina [4 ]
机构
[1] Jilin Univ, Coll Basic Med Sci, Changchun, Peoples R China
[2] Jilin Univ, Coll Basic Med Sci, Key Lab Pathobiol, Minist Educ, Changchun, Peoples R China
[3] First Hosp Jilin Univ, Dept Anesthesiol, Changchun, Peoples R China
[4] First Hosp Jilin Univ, Dept Pediat Respirat, Changchun, Peoples R China
关键词
lung adenocarcinoma; KIF20A; bioinformatics analysis; prognosis; therapeutic target; TUMOR MICROENVIRONMENT; CANCER; RESISTANCE; CELLS;
D O I
10.3389/fbioe.2022.993820
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The identification of prognostic and therapeutic biomarkers is essential to reduce morbidity and mortality from lung adenocarcinoma (LUAD). This study aimed to identify a reliable prognostic and therapeutic biomarker for LUAD using integrated bioinformatics. Based on the cancer genome atlas (TCGA) and genome-tissue expression (GTEx) analyses, KIF20A has been identified as the hub gene. Following validation using a series of cohorts, survival analysis, meta-analysis, and univariate Cox analysis was conducted. ESTIMATE and CIBERSORT algorithms were then used to study the association of KIF20A with the tumor microenvironment (TME) and the percentage of tumor-infiltrating immune cells (TICs). In vitro experiments were conducted to determine the function of KIF20A. Finally, there was a negative association between the expression of the KIF20A and overall survival, progression-free survival, and disease-free survival, which was confirmed by meta-analysis and COX analysis. Furthermore, KIF20A also had a potential role of altering the TME and TICs proportions in LUAD. Validations in vitro were performed on A549 and PC-9 cell lines, and we found that the knockdown of KIF20A exhibited inhibitory effects on cell proliferation, resulted in cell cycle arrest during the G2/M phase, and induced cellular apoptosis. Our study demonstrated that KIF20A could be utilized as a reliable prognostic marker and treatment target for LUAD. However, further studies are required to validate these findings.
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页数:20
相关论文
共 44 条
[1]   Relevance of Tumor-Infiltrating Immune Cell Composition and Functionality for Disease Outcome in Breast Cancer [J].
Bense, Rico D. ;
Sotiriou, Christos ;
Piccart-Gebhart, Martine J. ;
Haanen, John B. A. G. ;
van Vugt, Marcel A. T. M. ;
de Vries, Elisabeth G. E. ;
Schroeder, Carolien P. ;
Fehrmann, Rudolf S. N. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2017, 109 (01)
[2]   Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts [J].
Bhattacharyya, Sankar ;
Hossain, Dewan Md Sakib ;
Mohanty, Suchismita ;
Sen, Gouri Sankar ;
Chattopadhyay, Sreya ;
Banerjee, Shuvomoy ;
Chakraborty, Juni ;
Das, Kaushik ;
Sarkar, Diptendra ;
Das, Tanya ;
Sa, Gaurisankar .
CELLULAR & MOLECULAR IMMUNOLOGY, 2010, 7 (04) :306-315
[3]   Tumor Microenvironment: A Metabolic Player that Shapes the Immune Response [J].
Cassim, Shamir ;
Pouyssegur, Jacques .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (01)
[4]   ERBB2-Mutated Metastatic Non-Small Cell Lung Cancer: Response and Resistance to Targeted Therapies [J].
Chuang, Jody C. ;
Stehr, Henning ;
Liang, Ying ;
Das, Millie ;
Huang, Jane ;
Diehn, Maximilian ;
Wakelee, Heather A. ;
Neal, Joel W. .
JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (05) :833-842
[5]   Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer [J].
Elbaz, Mohamad ;
Nasser, Mohd W. ;
Ravi, Janani ;
Wani, Nissar A. ;
Ahirwar, Dinesh K. ;
Zhao, Helong ;
Oghumu, Steve ;
Satoskar, Abhay R. ;
Shilo, Konstantin ;
Carson, William E., III ;
Ganju, Ramesh K. .
MOLECULAR ONCOLOGY, 2015, 9 (04) :906-919
[6]   CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review [J].
Farhood, Bagher ;
Najafi, Masoud ;
Mortezaee, Keywan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (06) :8509-8521
[7]   The human kinesin-like protein RB6K is under tight cell cycle control and is essential for cytokinesis [J].
Fontijn, RD ;
Goud, B ;
Echard, A ;
Jollivet, F ;
van Marle, J ;
Pannekoek, H ;
Horrevoets, AJG .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (08) :2944-2955
[8]   The Role of Tumor Microenvironment in Cancer Immunotherapy [J].
Frankel, Timothy ;
Lanfranca, Mirna Perusina ;
Zou, Weiping .
TUMOR IMMUNE MICROENVIRONMENT IN CANCER PROGRESSION AND CANCER THERAPY, 2017, 1036 :51-64
[9]   The value of CEP55 gene as a diagnostic biomarker and independent prognostic factor in LUAD and LUSC [J].
Fu, Linhai ;
Wang, Haiyong ;
Wei, Desheng ;
Wang, Bin ;
Zhang, Chu ;
Zhu, Ting ;
Ma, Zhifeng ;
Li, Zhupeng ;
Wu, Yuanlin ;
Yu, Guangmao .
PLOS ONE, 2020, 15 (05)
[10]   Innate and adaptive immune cells in the tumor microenvironment [J].
Gajewski, Thomas F. ;
Schreiber, Hans ;
Fu, Yang-Xin .
NATURE IMMUNOLOGY, 2013, 14 (10) :1014-1022