Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (1): 188-197.DOI: 10.19852/j.cnki.jtcm.20221013.001
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Reveal the mechanisms of prescriptions for liver cancer' treatment based on two illustrious senior TCM physicians
WANG Bochuan1, ZHANG Yong2, ZHANG Qiuyun3, ZHANG Zhiqiang4, LUO Changyong5, WANG Zhendong1, BAI Chen1, WANG Yuhan1, GE Xueyi2, QIAN Ying3, YU He1(
), GU Xiaohong1()
- 1 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 10029, China
2 Liver Disease Branch, Shandong Hospital of Traditional Chinese Medicine, Jinan 250013, China
3 School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
4 Beijing Tcmages Pharmaceutical Co., Ltd., Beijing 101399, China
5 Dongfang Hospital Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100078, China
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Received:2022-05-05Accepted:2022-09-21Online:2023-02-15Published:2023-01-10 -
Contact:YU He,GU Xiaohong -
About author:Prof. GU Xiaohong, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 10029, China. guxiaohong1962@163.com. Telephone:+86-18810622544
Prof. YU He, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 10029, China. yuhe221@126.com;
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Supported by:National Key R&D Program of China Research on Inheritance and Innovation of Experience (Integration of Tao and Shu) of Illustrious Senior Traditional Chinese Medicine Practitioners by adopting Multiple Research Methods(2018YFC1704100);Research on Methodology System and Paradigms for Mining and Inheriting Illustrious Senior Traditional Chinese Medicine Practitioners’ Experience(2018YFC1704101)
Cite this article
WANG Bochuan, ZHANG Yong, ZHANG Qiuyun, ZHANG Zhiqiang, LUO Changyong, WANG Zhendong, BAI Chen, WANG Yuhan, GE Xueyi, QIAN Ying, YU He, GU Xiaohong. Reveal the mechanisms of prescriptions for liver cancer' treatment based on two illustrious senior TCM physicians[J]. Journal of Traditional Chinese Medicine, 2023, 43(1): 188-197.
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Figure 1 Workflow diagram TCMIP: Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine; OMIM: Online Mendelian Inheritance in Man; KEGG: Kyoto Encyclopedia of Genes and Genomes; GDC: Genomic Data Commons; TCGA: The Cancer Genome Atlas.
Figure 1 Workflow diagram TCMIP: Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine; OMIM: Online Mendelian Inheritance in Man; KEGG: Kyoto Encyclopedia of Genes and Genomes; GDC: Genomic Data Commons; TCGA: The Cancer Genome Atlas.
Figure 2 The screening process of CP (core prescription) for liver cancer The purple in the picture is the herb community of Physician 1, the green is the herb community of Physician 2, and the red is the non-core herbs used by the two Physicians.
Figure 2 The screening process of CP (core prescription) for liver cancer The purple in the picture is the herb community of Physician 1, the green is the herb community of Physician 2, and the red is the non-core herbs used by the two Physicians.
Table 1 Top 15 pathways in KEGG enrichment by two physicians
| KEGG | Pathway | Tyle | Physician |
|---|---|---|---|
| hsa04151 | PI3K (phosphatidylinositol-3-kinase)-Akt signaling pathway | Signal transduction | 1&2 |
| hsa04066 | HIF-1 (Hypoxia Inducible Factor 1) signaling pathway | Signal transduction | 1&2 |
| hsa04218 | Cellular senescence | Cell growth and death | 1&2 |
| hsa04210 | Apoptosis | Cell growth and death | 1&2 |
| hsa04657 | IL-17 (Interleukin 17) signaling pathway | Immune system | 1&2 |
| hsa04668 | TNF (Tumor Necrosis Factor) signaling pathway | Signal transduction | 1&2 |
| hsa04115 | p53 (Tumor Protein 53) signaling pathway | Cell growth and death | 1&2 |
| hsa04659 | Th17 cell differentiation | Immune system | 1&2 |
| hsa04926 | Relaxin signaling pathway | Endocrine system | 1&2 |
| hsa04625 | C-type lectin receptor signaling pathway | Immune system | 1&2 |
| hsa04380 | Osteoclast differentiation | Development and regeneration | 1&2 |
| hsa04660 | T cell receptor signaling pathway | Immune system | 1&2 |
| hsa04068 | FoxO signaling pathway | Signal transduction | 1 |
| hsa04620 | Toll-like receptor signaling pathway | Immune system | 1 |
| hsa04152 | AMPK (Adenosine 5-monophosphate(AMP)-activated protein kinase) signaling pathway | Signal transduction | 1 |
| hsa04010 | MAPK (mitogen-activated protein kinase) signaling pathway | Signal transduction | 2 |
| hsa04915 | Estrogen signaling pathway | Endocrine system | 2 |
| hsa04919 | Thyroid hormone signaling pathway | Endocrine system | 2 |
Table 1 Top 15 pathways in KEGG enrichment by two physicians
| KEGG | Pathway | Tyle | Physician |
|---|---|---|---|
| hsa04151 | PI3K (phosphatidylinositol-3-kinase)-Akt signaling pathway | Signal transduction | 1&2 |
| hsa04066 | HIF-1 (Hypoxia Inducible Factor 1) signaling pathway | Signal transduction | 1&2 |
| hsa04218 | Cellular senescence | Cell growth and death | 1&2 |
| hsa04210 | Apoptosis | Cell growth and death | 1&2 |
| hsa04657 | IL-17 (Interleukin 17) signaling pathway | Immune system | 1&2 |
| hsa04668 | TNF (Tumor Necrosis Factor) signaling pathway | Signal transduction | 1&2 |
| hsa04115 | p53 (Tumor Protein 53) signaling pathway | Cell growth and death | 1&2 |
| hsa04659 | Th17 cell differentiation | Immune system | 1&2 |
| hsa04926 | Relaxin signaling pathway | Endocrine system | 1&2 |
| hsa04625 | C-type lectin receptor signaling pathway | Immune system | 1&2 |
| hsa04380 | Osteoclast differentiation | Development and regeneration | 1&2 |
| hsa04660 | T cell receptor signaling pathway | Immune system | 1&2 |
| hsa04068 | FoxO signaling pathway | Signal transduction | 1 |
| hsa04620 | Toll-like receptor signaling pathway | Immune system | 1 |
| hsa04152 | AMPK (Adenosine 5-monophosphate(AMP)-activated protein kinase) signaling pathway | Signal transduction | 1 |
| hsa04010 | MAPK (mitogen-activated protein kinase) signaling pathway | Signal transduction | 2 |
| hsa04915 | Estrogen signaling pathway | Endocrine system | 2 |
| hsa04919 | Thyroid hormone signaling pathway | Endocrine system | 2 |
Figure 3 Herb targets show The connection between different herbal targets: blue-orange represents Huangqi (Radix Astragali Mongolici), and yellow represents Shuihonghuazi (Polygoni Orien-talis Fructus), red in the outer circle represents Baihuasheshecao (Herba Hedyotdis), blue represents Banzhilian (Herba Scutellariae Barbatae), green represents Danshen (Radix Salviae Miltio-rrhizae), purple represents Ezhu (Rhizoma Curcumae Phaeocaulis). The purple curve connects the same genes. The inner circle represents the gene list. The same genes of multiple herbs are shown in dark orange. Genes that have only appeared once are shown in light orange.
Figure 3 Herb targets show The connection between different herbal targets: blue-orange represents Huangqi (Radix Astragali Mongolici), and yellow represents Shuihonghuazi (Polygoni Orien-talis Fructus), red in the outer circle represents Baihuasheshecao (Herba Hedyotdis), blue represents Banzhilian (Herba Scutellariae Barbatae), green represents Danshen (Radix Salviae Miltio-rrhizae), purple represents Ezhu (Rhizoma Curcumae Phaeocaulis). The purple curve connects the same genes. The inner circle represents the gene list. The same genes of multiple herbs are shown in dark orange. Genes that have only appeared once are shown in light orange.
Figure 4 KEGG enrichment analysis Bubble plot of KEGG enrichment pathways. Each bubble represents a KEGG pathway. The size of the bubbles is related to the relative ratio of targets to total targets on each pathway, with larger bubbles representing more abundant genes. ?LogP shows the statistical significance of the P value. The larger the number, the more significant the P value. Establishing a network of pathways for the actions of core herbs
Figure 4 KEGG enrichment analysis Bubble plot of KEGG enrichment pathways. Each bubble represents a KEGG pathway. The size of the bubbles is related to the relative ratio of targets to total targets on each pathway, with larger bubbles representing more abundant genes. ?LogP shows the statistical significance of the P value. The larger the number, the more significant the P value. Establishing a network of pathways for the actions of core herbs
Figure 1 Patient characteristics
Figure 1 Patient characteristics
Figure 2 Herbal characteristics
Figure 2 Herbal characteristics
Figure 3 The subnetwork shows the gene pathway mechanism and regulation of the CP of two illustrious senior TCM physicians.
Figure 3 The subnetwork shows the gene pathway mechanism and regulation of the CP of two illustrious senior TCM physicians.
Table 1 Characteristics of top 20 herbs
| Herb | Frequency | Properties | Flavor |
|---|---|---|---|
| Baihuasheshecao (Hedyotis Diffusa) | 152 | Cold | Bitter,Sweet |
| Ezhu (Curcumae Rhizoma) | 139 | Warm | Pungent,Bitter |
| Banzhilian (Scutellariae Barbatae Herba) | 122 | Cold | Pungent,Bitter |
| Doukou (Amomi Fructus Rotundus) | 102 | Warm | Pungent |
| Chuanbeimu (Fritillariae Cirrhosae Bulbus) | 95 | Cold | Bitter,Sweet |
| Jineijin (Galli Gigerii Endothelium Corneum) | 89 | Mild | Sweet |
| Chonglou (Paridis Rhizoma) | 89 | Cold | Bitter |
| Huangqi (Astragali Radix) | 80 | Warm | Sweet |
| Shancigu (Cremastrae Pseudobulbus Pleiones Pseudobulbus) | 79 | Cool | Sweet,Pungent |
| Jixingzi (Impatientis Semen) | 77 | Warm | Bitter,Pungent |
| Dannanxing (Arisaema Cum Bile) | 72 | Cool | Bitter,Pungent |
| Fengfang (Vespaenidus) | 70 | Mild | Sweet |
| Muhudie (Oroxyli Semen) | 70 | Cool | Bitter,Sweet |
| Visciherba (Hujisheng) | 56 | Mild | Bitter |
| Danshen (Salviae Miltiorrhizae Radix Et Rhizoma) | 55 | Cold | Bitter |
| Yujin (Curcumae Radix) | 51 | Cold | Pungent,Bitter |
| Shuihonghuazi (Polygoni Orientalis Fructus) | 50 | Cold | Salty |
| Kushen (Sophorae Flavescentis Radix) | 46 | Cold | Bitter |
| Rehmanniae Radix (Dihuang) | 28 | Cold | Sweet,Bitter |
| Suanzaoren (Ziziphi Spinosae Semen) | 27 | Mild | Sweet,Sour |
Table 1 Characteristics of top 20 herbs
| Herb | Frequency | Properties | Flavor |
|---|---|---|---|
| Baihuasheshecao (Hedyotis Diffusa) | 152 | Cold | Bitter,Sweet |
| Ezhu (Curcumae Rhizoma) | 139 | Warm | Pungent,Bitter |
| Banzhilian (Scutellariae Barbatae Herba) | 122 | Cold | Pungent,Bitter |
| Doukou (Amomi Fructus Rotundus) | 102 | Warm | Pungent |
| Chuanbeimu (Fritillariae Cirrhosae Bulbus) | 95 | Cold | Bitter,Sweet |
| Jineijin (Galli Gigerii Endothelium Corneum) | 89 | Mild | Sweet |
| Chonglou (Paridis Rhizoma) | 89 | Cold | Bitter |
| Huangqi (Astragali Radix) | 80 | Warm | Sweet |
| Shancigu (Cremastrae Pseudobulbus Pleiones Pseudobulbus) | 79 | Cool | Sweet,Pungent |
| Jixingzi (Impatientis Semen) | 77 | Warm | Bitter,Pungent |
| Dannanxing (Arisaema Cum Bile) | 72 | Cool | Bitter,Pungent |
| Fengfang (Vespaenidus) | 70 | Mild | Sweet |
| Muhudie (Oroxyli Semen) | 70 | Cool | Bitter,Sweet |
| Visciherba (Hujisheng) | 56 | Mild | Bitter |
| Danshen (Salviae Miltiorrhizae Radix Et Rhizoma) | 55 | Cold | Bitter |
| Yujin (Curcumae Radix) | 51 | Cold | Pungent,Bitter |
| Shuihonghuazi (Polygoni Orientalis Fructus) | 50 | Cold | Salty |
| Kushen (Sophorae Flavescentis Radix) | 46 | Cold | Bitter |
| Rehmanniae Radix (Dihuang) | 28 | Cold | Sweet,Bitter |
| Suanzaoren (Ziziphi Spinosae Semen) | 27 | Mild | Sweet,Sour |
Table 2 Top 5 Pathway Categories
| KEGG PATHWAY | Frequency |
|---|---|
| Signal transduction | 24 |
| Immune system | 18 |
| Endocrine system | 16 |
| metabolism | 16 |
| Nervous system | 9 |
Table 2 Top 5 Pathway Categories
| KEGG PATHWAY | Frequency |
|---|---|
| Signal transduction | 24 |
| Immune system | 18 |
| Endocrine system | 16 |
| metabolism | 16 |
| Nervous system | 9 |
Table 3 Gene statistics related to survival in core herbs（p<0.01）
| Gene_Symbol | Gene_ID | coef | Hazard.Ratio(HR) | CI95 | P.Value |
|---|---|---|---|---|---|
| MT-CO1 | 4512 | -0.2663 | 0.7662 | 0.6388-0.9191 | 0.0041 |
| PPARGC1A | 10891 | -0.1854 | 0.8308 | 0.7280-0.9481 | 0.0060 |
| EPO | 2056 | 0.2606 | 1.2977 | 1.1746-1.4337 | 0.0000 |
| MMP1 | 4312 | 0.3369 | 1.4006 | 1.1914-1.6466 | 0.0000 |
| HMOX1 | 3162 | 0.2239 | 1.2510 | 1.1098-1.4101 | 0.0002 |
| CXCL8 | 3576 | 0.1620 | 1.1758 | 1.0780-1.2826 | 0.0003 |
| UGT1A8 | 54576 | 0.4095 | 1.5061 | 1.1686-1.9411 | 0.0016 |
| SERPINE1 | 5054 | 0.1267 | 1.1350 | 1.0468-1.2307 | 0.0021 |
| CA9 | 768 | 0.1152 | 1.1221 | 1.0417-1.2088 | 0.0024 |
| CDK4 | 1019 | 0.2561 | 1.2919 | 1.0813-1.5436 | 0.0048 |
| LGALS3 | 3958 | 0.1413 | 1.1517 | 1.0440-1.2706 | 0.0048 |
| HIF1A | 3091 | 0.2069 | 1.2298 | 1.0594-1.4276 | 0.0066 |
| ICAM1 | 3383 | 0.1625 | 1.1764 | 1.0455-1.3237 | 0.0069 |
| IFNB1 | 3456 | 5.1632 | 174.7229 | 4.0641-7511.6843 | 0.0071 |
Table 3 Gene statistics related to survival in core herbs（p<0.01）
| Gene_Symbol | Gene_ID | coef | Hazard.Ratio(HR) | CI95 | P.Value |
|---|---|---|---|---|---|
| MT-CO1 | 4512 | -0.2663 | 0.7662 | 0.6388-0.9191 | 0.0041 |
| PPARGC1A | 10891 | -0.1854 | 0.8308 | 0.7280-0.9481 | 0.0060 |
| EPO | 2056 | 0.2606 | 1.2977 | 1.1746-1.4337 | 0.0000 |
| MMP1 | 4312 | 0.3369 | 1.4006 | 1.1914-1.6466 | 0.0000 |
| HMOX1 | 3162 | 0.2239 | 1.2510 | 1.1098-1.4101 | 0.0002 |
| CXCL8 | 3576 | 0.1620 | 1.1758 | 1.0780-1.2826 | 0.0003 |
| UGT1A8 | 54576 | 0.4095 | 1.5061 | 1.1686-1.9411 | 0.0016 |
| SERPINE1 | 5054 | 0.1267 | 1.1350 | 1.0468-1.2307 | 0.0021 |
| CA9 | 768 | 0.1152 | 1.1221 | 1.0417-1.2088 | 0.0024 |
| CDK4 | 1019 | 0.2561 | 1.2919 | 1.0813-1.5436 | 0.0048 |
| LGALS3 | 3958 | 0.1413 | 1.1517 | 1.0440-1.2706 | 0.0048 |
| HIF1A | 3091 | 0.2069 | 1.2298 | 1.0594-1.4276 | 0.0066 |
| ICAM1 | 3383 | 0.1625 | 1.1764 | 1.0455-1.3237 | 0.0069 |
| IFNB1 | 3456 | 5.1632 | 174.7229 | 4.0641-7511.6843 | 0.0071 |
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