Mechanism underlying the effect of Liujunzi decoction (六君子汤) on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy

doi:10.19852/j.cnki.jtcm.2022.01.007

Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (1): 108-115.DOI: 10.19852/j.cnki.jtcm.2022.01.007

• Research Articles • Previous Articles Next Articles

Mechanism underlying the effect of Liujunzi decoction (六君子汤) on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy

Xiaoli XIN¹, Guodong WANG², Ru HAN¹, Yi JIANG¹, Chang LIU¹, Lingshuang LIU¹(), Zhenye XU¹()

1 Department of Oncology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
2 Department of Orthopedics, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 20032, China
3 Department of human resources, Shandong Academy of Occupational Health and Occupational Medicine, Jinan 250000, China

Received:2021-02-22 Accepted:2021-05-14 Online:2022-01-25 Published:2022-01-25
Contact: Lingshuang LIU,Zhenye XU
About author:XU Zhenye, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. xuzhenye1947@126.com
LIU Lingshuang, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. liuls107@163.com;
Supported by:
National Natural Science Foundation of China (NSFC) (Therapeutic Effect and Mechanism of Embryonic Lung Progenitor Cell Transplantation on Silicosis Fibrosis)(81903270);National Natural Science Foundation of China (NSFC) (Study on the Synergistic Effect and Mechanism of Yiqi Yangyin Jiedu Prescription Combined with Anti-CTLA-4 Mab in Inducing Anti-Lung Cancer Immune Response)(81703987);Jinan Science and Technology Project(Study of Therapy and Mechanisms of Embryonic Lung Stem Cell Transplantation on Silicosis Fibrosis)(201907019);Shanghai Science and Technology Commission (a Multicenter Randomized Controlled Study on Improving Prognosis of Patients With Stage ⅢA Non-Small Cell Lung Cancer By Liu Jiaxiang's Prescription for Qi-Yin Differentiation and Treatment)(19401971200);Emerging Frontier Technology Joint Research Project of Shanghai Shenkang Hospital Development Center (a Multicenter Randomized Controlled Double-Blind Study on the Prevention and Treatment of Postoperative Recurrence and Metastasis Of Stage ⅢA Non-Small Cell Lung Cancer By Liu Jiaxiang Qi-Yin Differentiation Method)(SHDC12018131);Major Project of Scientific Research and Innovation Plan of Shanghai Education Commission (Study on the Mechanism of Feyanning Prescription Against Lung Cancer Growth and Metastasis Derived from Jingqi Theory)(2017-01-07-00-10-E00064);Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Clinical Study of Yiqi Yangyin Jiedu Prescription Combined With Oxitinib in the Treatment of Advanced Lung Cancer With T790M Mutation)(AJ-37);Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Clinical Study of “Decubitus Chiropractic Therapy” in the Treatment of Vertebral Artery Type Cervical Spondylosis)(AJ-41);National Traditional Chinese Medicine Clinical Research Base Long-Yi-Xue-Zhe Nurturing Plan (Mechanism of Reversal of EGFR-Tkis Resistance Induced By HGF in Tumor-Bearing H1975-SCID Mice Based on Huachansu Injection)(LYTD-64)

Abstract

Abstract:

OBJECTIVE: To further clarify the anticancer mechanisms of Liujunzi decoction (六君子汤) and provide possible targets for the treatment of advanced-stage non-small cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoction-treated NSCLC patients receiving first-line chemotherapy.

METHODS: The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein–protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software.

RESULTS: A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine–cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development.

CONCLUSIONS: One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.

Key words: carcinoma, non-small-cell lung, antineoplastic agents, computational biology, RNA, small interfering, Liujunzi decoction

Xiaoli XIN, Guodong WANG, Ru HAN, Yi JIANG, Chang LIU, Lingshuang LIU, Zhenye XU. Mechanism underlying the effect of Liujunzi decoction (六君子汤) on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy[J]. Journal of Traditional Chinese Medicine, 2022, 42(1): 108-115.

Figures/Tables 12

References 34

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GO ID	Term	Percentage (%)	P value	Fold Enrichment	Number of DEGs
GO:0048666	neuron development	9.850	1.393×10^-3	2.444	17
GO:0048483	autonomic nervous system development	2.318	3.336×10^-3	13.214	4
GO:0010628	positive regulation of gene expression	13.326	4.019×10^-3	1.886	23
GO:0003382	epithelial cell morphogenesis	2.318	4.872×10^-3	11.563	4
GO:0007399	nervous system development	15.644	5.163×10^-3	1.726	27

GO ID	Term	Percentage (%)	P value	Fold Enrichment	Number of DEGs
GO:0048666	neuron development	9.850	1.393×10^-3	2.444	17
GO:0048483	autonomic nervous system development	2.318	3.336×10^-3	13.214	4
GO:0010628	positive regulation of gene expression	13.326	4.019×10^-3	1.886	23
GO:0003382	epithelial cell morphogenesis	2.318	4.872×10^-3	11.563	4
GO:0007399	nervous system development	15.644	5.163×10^-3	1.726	27

GO ID	Term	Percentage (%)	P value	Fold Enrichment		Number of DEGs
GO:0005578	proteinaceous extracellular matrix	4.056	0.042	2.735		7
GO:0005615	extracellular space	9.850	0.044	1.660		17
GO:0005576	extracellular region	24.335	0.045		1.281	42

GO ID	Term	Percentage (%)	P value	Fold Enrichment		Number of DEGs
GO:0005578	proteinaceous extracellular matrix	4.056	0.042	2.735		7
GO:0005615	extracellular space	9.850	0.044	1.660		17
GO:0005576	extracellular region	24.335	0.045		1.281	42

GO ID	Term	Percentage (%)	P value		Fold Enrichment	Number of DEGs
GO:0005509	Calcium ion binding	6.953	0.018		2.233	12
GO:0034584	piRNA binding	1.159	0.022		88.954	2
GO:0001228	Transcriptional activator activity, RNA polymerase Ⅱ transcription regulatory region sequence-specific binding	4.056		0.035	2.865	7
GO:0004252	Serine-type endopeptidase activity	3.476		0.042	3.140	6

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Mechanism underlying the effect of Liujunzi decoction (六君子汤) on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy

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Figures/Tables 12

References 34

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Gene	Expression regulated	Node degree	MCODE score	Gene	Expression regulated	Node degree	MCODE score
IL2	up	7	0.25	XCL1	down	3	2
PIWIL4	down	4	3	IL22RA1	up	3	0.5
DICER1	down	3	3	ARHGAP11A	down	3	0.5
PIWIL2	down	3	3	DCP1A	down	3	3
SAA1	up	3	2	GDNF	down	2	0.67

GO ID	Categories	Terms	FDR
GO:0010608	Biological process	posttranscriptional regulation of gene expression	7.88 × 10^-5
GO:0010629	Biological process	negative regulation of gene expression	0.0015
GO:0016070	Biological process	RNA metabolic process	0.0134
GO:1990904	Cellular component	ribonucleoprotein complex	0.00016
GO:0003723	Molecular function	RNA binding	0.0001

KEGG ID	Terms	matching proteins in network	FDR
HSA-211000	Gene Silencing by RNA	DICER1,PIWIL2,PIWIL4	7.77×10^-6
HSA-5601884	piRNA biogenesis	PIWIL2,PIWIL4	9.45×10^-5

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