Screening of Molecular Markers of Cisplatin Resistance in Lung Adenocarcinoma and Functional Verification Based on TCGA Database

WANG Lin; HUANG Zixian; YOU Chengcheng; TAN Shunzi; HUANG Liming; HUANG Yiling

doi:10.3971/j.issn.1000-8578.2022.21.1181

Cancer Research on Prevention and Treatment > 2022 > 49(6): 569-574. > DOI: 10.3971/j.issn.1000-8578.2022.21.1181

WANG Lin, HUANG Zixian, YOU Chengcheng, TAN Shunzi, HUANG Liming, HUANG Yiling. Screening of Molecular Markers of Cisplatin Resistance in Lung Adenocarcinoma and Functional Verification Based on TCGA Database[J]. Cancer Research on Prevention and Treatment, 2022, 49(6): 569-574. DOI: 10.3971/j.issn.1000-8578.2022.21.1181

Citation:

PDF (5600 KB)

Screening of Molecular Markers of Cisplatin Resistance in Lung Adenocarcinoma and Functional Verification Based on TCGA Database

1.
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang 443002, China
2.
Department of Pathology, China Three Gorges University Medical College, Yichang 443002, China
3.
Department of Gynaecology, Enshi Center Hospital, Enshi 445000, China

Funding:

National Natural Science Foundation of China 81374024

Yichang Medical and Health Scientific Research Project A21-2-048

Yichang Medical and Health Scientific Research Project A22-2-070

Open Fund of Hubei Provincial Key Laboratory of Tumor Microenvironment and Immunotherapy (China Three Gorges University) 2021KZL03

More Information

Corresponding author:
HUANG Yiling, E-mail: lotusyj@126.com
Received Date: October 17, 2021
Revised Date: January 04, 2022
Available Online: January 12, 2024

Graphical Abstract

Abstract

Abstract

Objective
To explore the related genes that play a key regulatory role in cisplatin resistance in lung adenocarcinoma.
Methods
Bioinformatics methods were used to download the differentially-expressed genes between cisplatin sensitive group and drug resistant group in patients with lung adenocarcinoma in TCGA database and GDSC database. GO function analysis and KEGG pathway enrichment analysis were carried out to analyze the differentially-expressed genes. The protein-protein interaction network was constructed and hierarchical cluster analysis was carried out to screen the key genes. The key genes were verified at the cell level by real-time fluorescence quantitative PCR and ELISA. Then the expression of the selected key gene in A549/DDP cells was silenced by siRNA and its sensitivity to cisplatin was detected.
Results
We screened out 178 differentially-expressed genes. After cluster analysis, CXCL9, CXCL10, NKX2-1 and SFTPA1 were regarded as the key genes of cisplatin resistance in lung adenocarcinoma. CXCL10 was temporarily selected for subsequent verification and function experiment. The mRNA expression of CXCL10 in A549/DDP cells was significantly higher than that in A549 cells (P < 0.001), and the expression of CXCL10 protein in the supernatant of A549/DDP cells was higher than that in A549 cells, which were consistent with the prediction of bioinformatics. The sensitivity of A549/DDP cells to DDP increased after silencing CXCL10 expression.
Conclusions
CXCL10 is a key gene to regulate cisplatin resistance in lung adenocarcinoma. Downregulating the expression of CXCL10 can become a potential target for reversing cisplatin resistance in lung adenocarcinoma.
- Lung adenocarcinoma,
- Bioinformatics,
- Differentially-expressed genes,
- Cisplatin resistance

FullText(HTML)

References (19)

References

[1]	Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2]	Ruiz-Cordero R, Devine WP. Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer[J]. Surg Pathol Clin, 2020, 13(1): 17-33. doi: 10.1016/j.path.2019.11.002
[3]	Ye T, Deng L, Xiang J, et al. Predictors of Pathologic Tumor Invasion and Prognosis for Ground Glass Opacity Featured Lung Adenocarcinoma[J]. Ann Thorac Surg, 2018, 106(6): 1682-1690. doi: 10.1016/j.athoracsur.2018.06.058
[4]	Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33. doi: 10.3322/caac.21708
[5]	Yang Y, Adebali O, Wu G, et al. Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues[J]. Proc Natl Acad Sci U S A, 2018, 115(21): E4777-E4785.
[6]	Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action[J]. Eur J Pharmacol, 2014, 740: 364-378. doi: 10.1016/j.ejphar.2014.07.025
[7]	Chen J, Chen QL, Wang WH, et al. Prognostic and predictive values of CXCL10 in colorectal cancer[J]. Clin Transl Oncol, 2020, 22(9): 1548-1564. doi: 10.1007/s12094-020-02299-6
[8]	Wennerberg E, Kremer V, Childs R, et al. CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo[J]. Cancer Immunol Immunother, 2015, 64(2): 225-235. doi: 10.1007/s00262-014-1629-5
[9]	Lee JH, Kim HN, Kim KO, et al. CXCL10 promotes osteolytic bone metastasis by enhancing cancer outgrowth and osteoclastogenesis[J]. Cancer Res, 2012, 72(13): 3175-3186. doi: 10.1158/0008-5472.CAN-12-0481
[10]	Tokunaga R, Zhang W, Naseem M, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation-A target for novel cancer therapy[J]. Cancer Treat Rev, 2018, 63: 40-47. doi: 10.1016/j.ctrv.2017.11.007
[11]	Meng Q, Zhang Y, Hu LG. Targeting Autophagy Facilitates T Lymphocyte Migration by Inducing the Expression of CXCL10 in Gastric Cancer Cell Lines[J]. Front Oncol, 2020, 10: 886. doi: 10.3389/fonc.2020.00886
[12]	Billottet C, Quemener C, Bikfalvi A. CXCR3, a double-edged sword in tumor progression and angiogenesis[J]. Biochim Biophys Acta, 2013, 1836(2): 287-295.
[13]	Mahmood TB, Chowdhury AS, Hossain MU, et al. Evaluation of the susceptibility and fatality of lung cancer patients towards the COVID-19 infection: A systemic approach through analyzing the ACE2, CXCL10 and their co-expressed genes[J]. Curr Res Microb Sci, 2021, 2: 100022.
[14]	Wang Y, Chen H, Zhang T, et al. Plasma cytokines interleukin-18 and C-X-C motif chemokine ligand 10 are indicative of the anti-programmed cell death protein-1 treatment response in lung cancer patients[J]. Ann Transl Med, 2021, 9(1): 33. doi: 10.21037/atm-20-1513
[15]	Ling CC, Ng KTP, Shao Y, et al. Post-transplant endothelial progenitor cell mobilization via CXCL10/CXCR3 signaling promotes liver tumor growth[J]. J Hepatol, 2014, 60(1): 103-109. doi: 10.1016/j.jhep.2013.08.017
[16]	Dimberg J, Skarstedt M, Löfgren S, et al. Protein expression and gene polymorphism of CXCL10 in patients with colorectal cancer[J]. Biomed Rep, 2014, 2(3): 340-343. doi: 10.3892/br.2014.255
[17]	Saahene RO, Wang J, Wang ML, et al. The role of CXC chemokine ligand 4/CXC chemokine receptor 3-B in breast cancer progression[J]. Biotech Histochem, 2019, 94(1): 53-59. doi: 10.1080/10520295.2018.1497201
[18]	Reynders N, Abboud D, Baragli A, et al. The Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment[J]. Cells, 2019, 8(6): 613. doi: 10.3390/cells8060613
[19]	Wu X, Sun A, Yu W, et al. CXCL10 mediates breast cancer tamoxifen resistance and promotes estrogen-dependent and independent proliferation[J]. Mol Cell Endocrinol, 2020, 512: 110866. doi: 10.1016/j.mce.2020.110866

Cited By

Cited by

Periodical cited type(1)

韩丽红，陈婧茹，林丽蓉，闫斌. 哺乳动物雷帕霉素靶蛋白与结直肠癌关系的生物信息学分析. 系统医学. 2023(05): 33-37 .

Other cited types(0)

Get Citation

PDF

XML

Article views (2328) PDF downloads (927) Cited by(1)

Turn off MathJax

Article Contents

Abstract

References

Screening of Molecular Markers of Cisplatin Resistance in Lung Adenocarcinoma and Functional Verification Based on TCGA Database