Feature Reports:Lung cancer

RNA sequencing⁃based research on the immune regulation mechanism of C⁃MET in lung cancer

  • Yue XU ,
  • Yanbin ZHANG ,
  • Shan. SU
Expand
  • *.Qingyuan People′s Hospital,Qingyuan 511436,China

Received date: 2023-06-23

  Online published: 2024-01-24

Abstract

Objective To analyze the immune regulation mechanism of C-MET expression in non-small cell lung cancer by transcriptome sequencing technology. Methods The C-MET expression of lung adenocarcinoma cell line (H1993) and lung squamous cell carcinoma cell line (EBC-1) with high C-MET expression was silenced using siRNA molecular interference technology. The differentially expressed genes (DEGs) before and after C-MET silencing were detected using transcriptome sequencing technology. The signal pathways and related genes of the immune microenvironment in which C-MET may participate in regulation were excavated through bioinformatics analysis. Finally, the co-culture technique of human immune cells with H1993 and EBC-1 was used to verify the effect of C-MET on immune factors such as INF-γ, INF-β and CXCL-10. Results We detected 505 DEGs in total using transcriptome sequencing.There were 38 differentially expressed genes in the C-MET regulation group before and after H1993, 24 upregulated differentially expressed genes, and 14 downregulated differentially expressed genes, respectively. There are a total of 467 differentially expressed genes in the C-MET regulation group of EBC-1, 347 upregulated differentially expressed genes, and 121 downregulated differentially expressed genes, respectively. KEGG analysis of differential genes suggested that C-MET expression might participate in the regulation of immune cell regulatory factors through the IL-17 signaling pathway, white blood cell differentiation, cytokine receptor activity, cell cycle, cytokine receptor activity, and cytokine-cytokine receptor interaction. The effect of C-MET on immune factor secretion was verified using the co-culture technique of lung cancer cells and human immune cells, and the results of Rt-qPCR assay suggested,the mRNA transcriptional level of INF-γ in PBMC co-cultured with the C-MET high expression group was 77 times that of the low expression group, and the mRNA transcriptional level of CXCL-10 was 1.6 times that of the low expression group. The mRNA transcriptional level of INF--β was twice as high as that of the low expression group. Conclusion C-MET expression may participate in the regulation of tumor surrounding immune microenvironment through IL-17 signaling pathway, leukocyte differentiation, and cytokine receptor activity pathway.

Cite this article

Yue XU , Yanbin ZHANG , Shan. SU . RNA sequencing⁃based research on the immune regulation mechanism of C⁃MET in lung cancer[J]. The Journal of Practical Medicine, 2024 , 40(1) : 7 -12 . DOI: 10.3969/j.issn.1006-5725.2024.01.002

References

1 XIA C, DONG X, LI H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants [J]. Chin Med J (Engl),2022,135(5):584-590.
2 SIEGEL R L, MILLER K D, WAGLE N S, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023,73(1):17-48.
3 SAIGI M, ALBURQUERQUE-BEJAR J J, LEER-FLORIN A MC, et al. MET-Oncogenic and JAK2-Inactivating Alterations Are Independent Factors That Affect Regulation of PD-L1 Expression in Lung Cancer[J]. Clin Cancer Res,2018,24(18):4579-4587.
4 ZHANG Y, YANG Q, ZENG X, et al. MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING[J]. Cancer Discov, 2021,11(11):2726-2737.
5 BENKHOUCHA M, MOLNARFI N, KAYA G, et al. Identification of a novel population of highly cytotoxic c-Met-expressing CD8(+) T lymphocytes[J]. EMBO Rep, 2017,18(9):1545-1558.
6 YOSHIMURA K, INOUE Y, TSUCHIYA K, et al. Elucidation of the relationships of MET protein expression and gene copy number status with PD-L1 expression and the immune microenvironment in non-small cell lung cancer[J]. Lung cancer, 2020,141:21-31.
7 YOSHIDA R, SAIGI M, TANI T, et al. MET-Induced CD73 Restrains STING-Mediated Immunogenicity of EGFR-Mutant Lung Cancer[J]. Cancer Res, 2022,82(21):4079-4092.
8 EDWARDS S C, HEDLEY A, HOEVENAAR W H M, et al. PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing γδ T cells[J]. J Exp Med, 2023,220(2):e20211431.
9 GU C, WU L, LI X. IL-17 family: cytokines, receptors and signaling[J]. Cytokine, 2013,64(2):477-485.
10 BERRY S P D, DOSSOU C, KASHIF A, et al. The role of IL-17 and anti-IL-17 agents in the immunopathogenesis and management of autoimmune and inflammatory diseases[J]. Int Immunopharmacol, 2022,PMID:.
11 PATIN E C, SOULARD D, FLEURY S, et al. Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of Protumoral IL17A-Producing γδT Cells in Breast Cancer[J]. Cancer Res, 2018,78(1):195-204.
12 ZHIZHU ZHANG, RICHMOND ANN, CHI YAN. Immunomodulatory Properties of PI3K/AKT/mTOR and MAPK/MEK/ERK Inhibition Augment Response to Immune Checkpoint Blockade in Melanoma and Triple-Negative Breast Cancer[J]. Int J Mol Sci,2022,23(13):7353.
13 ANTONELLI A, FERRARI S M, GIUGGIOLI D, et al. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases[J]. Autoimmun Rev, 2014,13(3):272-280.
14 SCIASCIA S, BERTOLACCINI M L, BALDOVINO S, et al. Central nervous system involvement in systemic lupus erythematosus: Overview on classification criteria[J]. Autoimmun Rev, 2013,12(3):426-429.
15 JORGOVANOVIC D, SONG M, WANG L, et al. Roles of IFN-γin tumor progression and regression: a review[J]. Biomark Res,2020,8:49.
16 GAO Y, YANG J, CAI Y, et al. IFN-γ-mediated inhibition of lung cancer correlates with PD-L1 expression and is regulated by PI3K-AKT signaling[J]. Int J Cancer, 2018,143(4):931-943.
17 XU Y H, LI Z L, QIU S F. IFN-γ Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin β3-Mediated NF-κB Signaling[J]. Transl Oncol, 2018,11(1):182-192.
18 FANG C, WENG T, HU S, et al. IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells[J]. Oncoimmunology, 2021,10(1):1962591.
19 FLIES A S, LYONS A B, CORCORAN L M, et al. PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment[J]. Front Immunol, 2016,7:581.
20 AYERS M, LUNCEFORD J, NEBOZHYN M, et al. IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade[Z]. J Clin Invest, 2017: 127, 2930-2940.
21 DANGAJ D, BRUAND M, GRIMM A J, et al. Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors[J]. CANCER CELL, 2019,35(6):885-900.
Outlines

/