The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of “cancerous toxin” in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

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Colorectal Cancer, Gut Microbiota and Traditional Chinese Medicine: A Systematic Review

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500385 ◽

2021 ◽

pp. 1-24

Author(s):

Hui Zhao ◽

Man He ◽

Meng Zhang ◽

Qiang Sun ◽

Sha Zeng ◽

...

Keyword(s):

Colorectal Cancer ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Gut Microbiota ◽

Microbial Colonization ◽

Mucosal Barrier ◽

Cancer Genes ◽

Barrier Dysfunction ◽

Herbal Compound ◽

Chinese Herbal Compound

Based on the study and research on the pathogenesis of colorectal cancer, the types and functions of gut microbiota, and its role in guiding and regulating the occurrence and development of diseases, we have explored the mechanism of traditional Chinese medicine in the treatment of colorectal cancer by regulating the gut microbiota. Genetic variation, abnormal responses of innate and adaptive immunity, mucosal barrier dysfunction, imbalance of intestinal microbial colonization, personal and environmental risk factors are the main pathogenesis of colorectal cancer. The gut microbiota mainly includes Sclerotium (including Clostridium, Enterococcus, Lactobacillus and Ruminococcus) and Bacteroides (including Bacteroides and Prevotella), which have biological antagonism, nutrition for the organism, metabolic abilities, immune stimulation, and ability to shape cancer genes functions to body. The gut microbiota can be related to the health of the host. Current studies have shown that Chinese herbal compound, single medicinal materials, and monomer components can treat colorectal cancer by regulating the gut microbiota, such as Xiaoyaosan can increase the abundance of Bacteroides, Lactobacillus, and Proteus and decrease the abundance of Desulfovibrio and Rickerella. Therefore, studying the regulation and mechanism of gut microbiota on colorectal cancer is of great benefit to disease treatment.

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Gut Microbiota, Fusobacteria, and Colorectal Cancer

Diseases ◽

10.3390/diseases6040109 ◽

2018 ◽

Vol 6 (4) ◽

pp. 109 ◽

Cited By ~ 17

Author(s):

Dervla Kelly ◽

Liying Yang ◽

Zhiheng Pei

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Inflammatory Responses ◽

Tumor Development ◽

Host Responses ◽

Future Research ◽

Bacterial Microbiota ◽

Promote Tumor Growth ◽

Tumor Environment ◽

Protective Strategies

The gut microbiota has emerged as an environmental contributor to colorectal cancer (CRC) in both animal models and human studies. It is now generally accepted that bacteria are ubiquitous colonizers of all exposed human body surfaces, including the entire alimentary tract (5). Recently, the concept that a normal bacterial microbiota is essential for the development of inflammation-induced carcinoma has emerged from studies of well-known colonic bacterial microbiota. This review explores the evidence for a role of fusobacteria, an anaerobic gram-negative bacterium that has repeatedly been detected at colorectal tumor sites in higher abundance than surrounding histologically normal tissue. Mechanistic studies provide insight on the interplay between fusobacteria, other gut microbiota, barrier functions, and host responses. Studies have shown that fusobacteria activate host inflammatory responses designed to protect against pathogens that promote tumor growth. We discuss how future research identifying the pathophysiology underlying fusobacteria colon colonization during colorectal cancer may lead to new therapeutic targets for cancer. Furthermore, disease-protective strategies suppressing tumor development by targeting the local tumor environment via bacteria represent another exciting avenue for researchers and are highlighted in this review.

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Identification and Validation of a Glycolysis Related Metabolic Reprogramming Gene Signature for Predicting Survival in Colon Cancer Patients

10.21203/rs.3.rs-916034/v1 ◽

2021 ◽

Author(s):

Gang Liu ◽

Xiaowang WU ◽

Jian Chen

Keyword(s):

Colon Cancer ◽

Prediction Model ◽

Cox Regression ◽

Malignant Tumors ◽

Gene Signature ◽

Metabolic Reprogramming ◽

Risk Scores ◽

Cox Regression Analysis ◽

Prognosis Model ◽

The Relationship

Abstract Background Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with high mortality rate. Because of malignancy and easily metastasis feather, and limited treatments, the prognosis of CC remains poor. Glycolysis is a metabolic process of glucose in anoxic environments which is an important way to provide energy for tumor. The role of glycolysis in CC largely remains unknown and is necessary to be explored. Method In our study, we analyzed glycolysis related genes expression in CC, patients gene expression and corresponding clinical data were downloaded from GEO dataset, glycolysis related genes sets were collected from Msigdb. Through COX regression analysis, prognosis model based on glycolysis-related genes was established. The efficacy of gene model was tested by Survival analysis, ROC analysis and PCA analysis. Furthermore, the relationship between risk scores and clinical characteristic was researched. Results Our findings identified 13 glycolysis related genes (NUP107, SEC13, ALDH7A1, ALG1, CHPF, FAM162A, FBP2, GALK1, IDH1, TGFA, VLDLR, XYLT2 and OGDHL) consisted prognostic prediction model with relative high accuracy. The relationship between prediction model and clinical feathers were specifically studied, results showed age > 65years, TNM III-IV, T3-4, N1-3, M1 and high-risk score were independent prognostic risk factors with poorer prognosis. Finally, model genes were significantly expressed and EMT were activated in CC patients. Conclusion This study provided a new aspect to advance our understanding in the potential mechanism of glycolysis in CC.

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High expression of Wnt7a protein predicts a poor survival in patients with colorectal carcinoma

10.21203/rs.3.rs-19428/v1 ◽

2020 ◽

Author(s):

Congcong Li ◽

Peilin Cui ◽

Xiaowei Dou ◽

Hongli Li ◽

Jiahuan Sun ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Malignant Tumors ◽

Integration Site ◽

Normal Mucosa ◽

Lymph Node Involvement ◽

Colorectal Adenomas ◽

Future Research ◽

Colorectal Mucosa ◽

Staining Score

Abstract Background: Colorectal cancer is one of the most common malignant tumors in China, and the number of new cases and the number of cases of deaths has increased annually. However, its pathogenesis is still unclear. Wnt7a is a member of the wingless-type MMTV integration site family, and it plays an important role in tumorigenesis and development by controlling cell proliferation and differentiation as a secreted glycoprotein. Whether Wnt7a has the properties of an oncogene or not is an important focus for future research as this target has diverse roles in different tumors.Methods: Wnt7a protein expression in normal colorectal mucosa and colorectal tumors was detected via immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were used to explore the associations between Wnt7a staining score and various clinical parameters.Results: Wnt7a was strongly expressed in colorectal cancer tissues but weakly expressed in adjacent normal mucosa and colorectal adenomas. The level of Wnt7a expression was correlated with lymph node involvement (P < 0.001), Duke stage (P < 0.001), and cell differentiation (P < 0.001). Knockdown of Wnt7a inhibits proliferation of colon cancer cells and inhibits the ability of both colon cancer cell lines to migrate.Conclusions: Collectively, our results present evidence that Wnt7a is associated with an unfavorable prognosis of colorectal cancer.

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Probiotics and Colon Cancer

Microorganisms ◽

10.3390/microorganisms7030066 ◽

2019 ◽

Vol 7 (3) ◽

pp. 66 ◽

Cited By ~ 24

Author(s):

Lorenzo Drago

Keyword(s):

Colon Cancer ◽

Radiation Therapy ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Immune Modulation ◽

Average Frequency ◽

Scientific Interest ◽

Positive Action ◽

Bowel Movements ◽

The Relationship

Literature has recently highlighted the enormous scientific interest on the relationship between the gut microbiota and colon cancer, and how the use of some selected probiotics can have a future impact on the adverse events which occur during this disease. Although there is no clear evidence to claim that probiotics are effective in people with cancer, recent reviews have found that probiotics can significantly reduce the incidence of diarrhea and the average frequency of daily bowel movements. However, most of this evidence needs to be more clinically convincing and further discussed. Undoubtedly, some probiotics, when properly dosed and administered, can have a strong rebalance effect on the gut microbiota and as a consequence a possible positive action on immune modulation of the gastrointestinal tract and on inflammation of the intestinal mucosa. Many recent findings indeed support the hypothesis that the daily use of some selected probiotics can be a feasible approach to effectively protect patients against the risk of some severe consequences due to radiation therapy or chemotherapy. This paper aims to review the most recent articles in order to consider a possible adjuvant approach for the use of certain well-balanced probiotics to help prevent colon cancer and the adverse effects caused by related therapies.

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Association of dietary fibre intake and gut microbiota in adults

British Journal Of Nutrition ◽

10.1017/s0007114518002465 ◽

2018 ◽

Vol 120 (9) ◽

pp. 1014-1022 ◽

Cited By ~ 20

Author(s):

Daniel Lin ◽

Brandilyn A. Peters ◽

Charles Friedlander ◽

Hal J. Freiman ◽

James J. Goedert ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Gut Microbiota ◽

Dietary Fibre ◽

Meta Analysis ◽

Microbiota Composition ◽

Fibre Intake ◽

Dietary Fibre Intake ◽

The Relationship ◽

Gut Microbiota Composition

AbstractIncreasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.

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The Role of the Gut Microbiome in Colorectal Cancer

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0037-1602239 ◽

2018 ◽

Vol 31 (03) ◽

pp. 192-198 ◽

Cited By ~ 14

Author(s):

Grace Chen

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Microbial Community ◽

Gut Microbiota ◽

Gut Microbiome ◽

Intestinal Health ◽

Genotoxic Effects ◽

Bacterial Populations ◽

Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

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SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

BMC Cancer ◽

10.1186/s12885-021-08536-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shaokun Wang ◽

Li Pang ◽

Zuolong Liu ◽

Xiangwei Meng

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Immune Cells ◽

Immune Cell ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

The Relationship

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

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The Impact of KPNA2 on Prognosis of Colorectal Cancer Patients: A Meta-Analysis

10.21203/rs.3.rs-1235315/v1 ◽

2022 ◽

Author(s):

Zhangzhe Yan ◽

Mingang He ◽

Haoxin Shi ◽

Haipeng Wang ◽

Miao Qin ◽

...

Keyword(s):

Colorectal Cancer ◽

Malignant Tumors ◽

Hot Spot ◽

Meta Analysis ◽

Tumor Stage ◽

Medical Database ◽

High Level ◽

Colorectal Cancer Patients ◽

The Impact ◽

The Relationship

Abstract Background and purpose: Colorectal cancer (CRC) is one of the most common malignant tumors with the highest mortality globally. At present, there is no exact biomarker to predict the prognosis and clinicopathological monitoring of CRC patients. Recent studies on the relationship of Karyopherin α 2 (KPNA2) expression and the prognosis of CRC has gradually become a hot spot while the results are still controversial. The aim of this study was to analyze and assess the prognostic role of KPNA2 in CRC patients. Methods: PubMed, Web of Science, Medline, EMBASE, CNKI, Wanfang, VIP, and Chinese Medical Database were systematically searched. The cohort study of high-level expression of KNPA2 and low-level expression of KPNA2 in CRC patients was included, the relevant data were extracted and the literature quality was evaluated. At the same time, the relationship between KPNA2 expression level and the overall survival (OS), the clinicopathological stage of CRC patients was studied. Meta-analysis was carried out by Stata MP 17.0 (Stata Corporation, College Station, TX, USA) software. Results: A total of 7 cohort studies involving 1166 patients were included. The analysis results showed that higher KPNA2 expression was significantly associated with higher tumor stage (OR=1.90, 95% CI 1.42–2.54), higher degree of tumor invasion (OR=2.14，95% CI 1.55-2.94), more lymph node metastasis (OR=2.20, 95% CI 1.68-2.88) and more distant metastasis (OR=3.66，95% CI 1.81-7.40). Moreover, higher KPNA2 expression was significantly associated with the shorter OS (HR=2.31, 95%CI 1.46-3.68).Conclusion: KPNA2 overexpression is an unfavorable prognostic factor for CRC patients. It could serve as a prognostic biomarker and as a potential therapeutic target for CRC.

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