| Objective1.Retrospectively analyzing the clinical characteristics of patients with left or right colon cancer and the underlying rules and differences of traditional Chinese medicine(TCM)prescriptions.2.Based on clustering algorithm and Apriori association rules algorithm,the present study mined the core prescription combinations and prescription rules of traditional Chinese medicine prescriptions for patients with left or right colon cancer in clinical practice.3.To analyze the potential pharmacological mechanism of the typical prescriptions for left or right colon cancer in clinical practice by network pharmacology.MethodsThe First Part:1.Retrospective analyzing the clinical characteristics of patients with left or right colon cancer in our hospital’s clinical practice and their differences in TCM prescriptions and prescription rules.Diagnosis criteria of colon cancer was referred to the International Union Against Cancer(UICC)TNM and clinical staging standards for colorectal cancer(eighth edition)and the diagnostic criteria of the Colorectal Cancer Diagnosis and Treatment Plan of the Key Specialty Collaboration Group of the State Administration of TCM.Colon patients who admitted to the oncology ward,gastrointestinal surgery ward or anorectal surgery ward in The First Affiliated Hospital of Guangzhou University of TCM from January 1,2017 to June 30,2020 and met the inclusion criteria were enrolled.2.Record the baseline data of the patient’s first hospitalization,including: gender,age,surgical status,pathological type,Kamofsky Performance Status(KPS)score,clinical stage,etc.,as well as the information of TCM prescriptions used by the chief physician during the patient’s first three hospitalizations.Taking the location of colon cancer as a stratification factor,statistical analysis of the differences in clinical baseline data and the differences in the rules of prescriptions were performed.3.Based on the cluster analysis algorithm,the R package apclustera was applied to determine the optimal number of clusters for the prescription data of left and right colon cancer.R package cluster was applied to perform K-means cluster analysis for the prescriptions’ data.In addition,R package factoextra was applied to visualize the clustering results.4.Based on the Apriori association rule algorithm to analyze the rule of TCM prescriptions for the prevention and treatment of left and right colon cancer.The R package arules was used to analyze and filter the association rules.Cytoscape 3.7.2 was used to visualize the association rules network.The Second Part:1.The colon cancer’s disease-related target genes were obtained from the Gene Cards database.The R package TCGAbiolinks was utilized to download the transcriptome data and clinical data of colon cancer from The Cancer Genome Atlas(TCGA)database.R software package DEseq2 was used for differential analysis to screen the differential genes of left and right colon cancer respectively.The two parts of target genes obtained were matched,and the left and right colon cancer’s disease-related targets gene were identified.2.The compounds and target genes of "Scutellaria barbata-Pinellia ternata-Tangerine peel",the typical prescription for left colon cancer,and "Sanguisorba-Licorice-Sophora japonica.L",the typical prescription for right colon cancer,were obtained from Batman-TCM database.Subsequently,the target genes of the typical prescriptions for left and right colon cancer were combined and mapped with the target genes of the left and right colon cancer respectively.Cytoscape 3.7.2 was used to construct a “drugs-compounds-diseases-target genes” network.The key compounds of the typical prescriptions for left and right colon cancer were screened separately according to the network topology value.3.The STRING database was applied to obtain the protein interaction relationship between the target genes of the typical prescriptions for left or right colon cancer,and the protein-protein interaction(PPI)network was constructed respectively.Next,the hub target genes were screened according to the network topology value.R package Cluster Profiler was used to perform Gene Ontology(GO)and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway analysis for the target genes of typical prescriptions for left or right colon cancer to identify underlying their pharmacological mechanisms for of the typical prescriptions for colon cancer.ResultThe First Part:1.Clinical characteristics analysis:(1)Among the 154 patients included in this study,81 patients with left colon cancer,accounting for 52.6%,and 73 patients with right colon cancer,accounting for 47.4%.The proportion of left colon cancer was higher than that of right colon cancer.There were 38 cases(52%)of right colon cancer in women,more than 35 cases(48%)in men.(2)The proportion of patients with KPS score more than 50 in left colon cancer at first admission was higher than that in patients with right colon cancer(96% VS 90%),but there was no statistical difference between the two groups(P>0.05);(3)The proportion of poorly differentiated adenocarcinoma in patients with left colon cancer was higher than that of patients with right colon cancer(22% VS 8.6%,P=0.04),while the proportion of moderately differentiated adenocarcinoma in patients with right colon cancer was higher than that in patients with left colon cancer(86% VS 63%,P<0.01);(4)The top five metastatic sites of patients with left colon cancer were: abdominal lymph nodes(37%)> liver(30%)> lung(16%)> bone(5.5%)> peritoneum(2.8%),while in patients with right colon cancer they were: liver(30%)> abdominal lymph nodes(27%)> lung(17%)>peritoneum(6.8%)> bone(2.9%).There was no significant statistical difference in the distribution of overall metastasis sites between two groups(P>0.05);(5)The first type of syndrome of both left and right colon cancer patients was internal phlegm-dampness retention syndrome(56% VS 42%),while the proportion of patients with left colon cancer in stagnant toxin syndrome was higher than that of right colon cancer(17%VS 12%);Right colon cancer patients had a higher proportion of qi and blood deficiency syndrome(26% VS 16%),spleen and kidney yang deficiency syndrome(15% VS 8.6%),and liver and kidney yin deficiency syndrome than patients with left colon cancer(4.1% VS2.5%).Overall,deficiency syndrome was more common in patients with right colon cancer than with left colon cancer(45.1% VS 27.1%).There was no statistically significant difference in TCM syndrome type between left and right colon cancer patients(P>0.05).2.The analysis of the prescriptions’ rules for the left and right colon cancer:(1)In terms of the application of TCM prescriptions,there were 17 kinds of prescriptions commonly used by patients with left and right colon cancer,of which 13 were for left colon cancer and 10 were for right colon cancer.Overall,the selection of prescriptions for patients with left colon cancer was more diverse than that for right colon cancer;(2)In terms of the four qi and five flavors of TCM,the proportion of cold Chinese medicine used for patients with left colon cancer was higher than that for patients with right colon cancer(57% VS 53.6%),while the proportion of warm Chinese medicine for patients with right colon cancer was higher than that for patients with right colon cancer(46.9% VS43.2%).Besides,both left and right colon cancers medications were ranked first in the proportion of sweet Chinese medicine(32% VS 35%);the proportion of pungent and acidic Chinese medicines for left colon cancer was higher than that for right colon cancer(26% VS23%;5.3% VS 5.1%),whereas the proportion of sweetness and saltiness(5.6% VS 5.7%)of Chinese medicine for right colon cancer was higher than that for left colon cancer;(3)There was totally 270 kinds of Chinese medicine applied the left and right colon cancer prescriptions,and a total of 44 typical Chinese medicines shared by the two groups.There were 4 typical Chinese medicines unique to left colon cancer,and 13 typical Chinese medicines unique to right colon cancer.(4)The cluster analysis results showed that the core drug combinations for left and right colon cancer were all 18 types.The core combination of left colon cancer highlighted the functions of clearing heat and removing toxicity and promoting qi and blood circulation.Representative core combinations of Chinese medicines included: "Edible tulip-Barbed skullcap herb-Herba sarcandrae-Solanum nigrum","Curcuma zedoaria-Szechuan lovage rhizome-fructus aurantii-Angelica sinensis-Bupleurum chinense",etc..The overall effect of the core prescriptions for right colon cancer was characterized by strengthening the spleen and qi,nourishing and enriching blood.The core combination of representative Chinese medicines included: "Angelica sinensis-Astragalus membranaceus" and "Oldenlandia diffusa-Ficus hirta-Chinese yam",etc..(5)Association rule analysis shows that there were 22 core association rules for left colon cancer prescriptions,and representative association rules include: "Scutellaria barbataFrench Pinellia-Tangerine Peel" and "Poria-Mairei Yew-Atractylodes" etc.;there were 37 core association rules for right colon cancer,and representative association rules include "Poria-Atractylodes" and "Diyus-Glycyrrhiza-Sophora japonicus" and others.The Second Part:Network pharmacological analysis of typical prescriptions for left and right colon cancer:(1)The key anti-cancer compound of "Scutellaria barbata-Pinellia ternata-Tangerine peel",the typical prescription for left colon cancer,mainly include: Ephedrine,GammaAminobutyric Acid,and Trigonelline.Their hub target genes included: ESR1,FASLG,KITLG,BCL2L1 and CD28;The biological process of the typical prescription treating left colon cancer included: response to oxygen levels,regulation of endopeptidase activity and regulation of apoptotic signaling pathway;The KEGG pathway of the typical prescription treating left colon cancer included MAPK signaling pathway,Ras signaling pathway and PI3K-Akt signaling pathway.(1)The key anti-cancer compound of "Sanguisorba-Licorice-Sophora japonica.L",the typical prescription for right colon cancer,mainly include Betulin,Tetrahydropalmatine and Ursolic acid.Their hub target genes included: IFNG,MAPK3,PTGS2,KL and CYP27A1;The biological process of the typical prescription treating right colon cancer included steroid metabolic process,positive regulation of defense response and positive regulation of inflammatory response;The KEGG pathway of the typical prescription treating right colon cancer included: IL-17 signaling pathway,VEGF signaling pathway and TNF signaling pathway.Conclusion1.In this study,the left and right colon cancer patients have different characteristics and proportions in terms of incidence,gender,KPS score,tumor metastasis site and TCM syndrome type.Overall,deficiency syndrome was more common in patients with right colon cancer than in patients with left colon cancer.These clinical factors might have a impact on TCM syndrome differentiation and treatment,which is worthy of further discussion and attention.2.There were some differences in prescription and drug characteristic between the TCM treatment for left and right colon cancer in clinical practice.By data mining algorithms 18 representative core drug combinations for left and right colon cancer respectively were identified.The core combination of left colon cancer highlighted the functions of clearing heat and removing toxicity and promoting qi and blood circulation,while the overall effect of the core prescriptions for right colon cancer was characterized by strengthening the spleen and qi,nourishing blood and stopping bleeding.A total of 59 core drug association rules were obtained.There were 22 core association rules for left colon cancer prescriptions,and representative association rules was "Scutellaria barbata-Pinellia ternata-Tangerine peel";there were 37 core association rules for right colon cancer,and representative association rules was "Sanguisorba-Licorice-Sophora japonica.L".These results reflected the different characteristics of TCM in the treatment of left and right colon cancer and could provide a strategic reference for the treatment of left and right colon cancer in clinical practice.3.Network pharmacology analysis showed that the typical prescriptions for left and right colon cancers "Scutellaria barbata-Pinellia ternata-Tangerine peel" and "SanguisorbaLicorice-Sophora japonica.L" could treat colon cancer through the features of multiple compounds,multiple targets,and multiple pathways.The results of the present study could lay a theoretical foundation for further fundamental researches. |
PDF Full Text Request