Ulcerative colitis-associated colorectal cancer

The association between ulcerative colitis(UC) and colorectal cancer(CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC(UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, lowgrade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC.

Magnifying chromoscopy, a novel and useful technique for colonoscopy in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. The degree of inflammation as assessed by conventional colonoscopy is a reliable parameter of disease activity. However, even when conventional colonoscopy suggests remission and normal mucosal findings, microscopic abnormalities may persist, and relapse may occur later. Patients with long-standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer. Ulcerative colitis-associated colorectal cancer is characterized by an early age at onset, poorly differentiated tumor cells, mucinous carcinoma, and multiple lesions. Early detection of dysplasia and colitic cancer is thus a prerequisite for survival. A relatively new method, magnifying chromoscopy, is thought to be useful for the early detection and diagnosis of dysplasia and colitic cancer, as well as the prediction of relapse.

Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing

Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.

Macrophage involvement in the pathological evolution of ulcerative colitis-associated colon cancer and progress of related traditional Chinese medicine drug interventions

Intestinal macrophages are essential players in intestinal inflammation and intestinal immune homeostasis.Intestinal macrophages have the ability to polarize into two distinct phenotypes based on various environmental signals.These phenotypes include the typically activated pro-inflammatory M1 phenotype and the alternatively activated anti-inflammatory M2 phenotype.Under normal circumstances,intestinal macrophages prevent inflammatory damage to the gut.However,when genetic and environmental factors influence the polarization of intestinal macrophages,it can lead to an imbalance in M1/M2 macrophage activation and subsequently an imbalance in the control of intestinal inflammation.It transforms physiological inflammation into pathological intestinal damage.In patients with ulcerative colitis-associated cancer(UC-CRC),intestinal inflammatory disorders are closely associated with intestinal M1/M2 macrophage polarization imbalance.Consequently,restoring the polarization equilibrium of M1/M2 macrophages might be an evidence of traditional Chinese medicine in the treatment of UC-CRC,the pivotal role o effective measure to prevent and treat UC-CRC.This paper aims to examine the clinicalf macrophage polarization in UC-CRC pathogenesis,and the potential mechanisms of traditional Chinese medicine in regulating macrophage polarization to treat UC-CRC.Our goal is to provide novel insights into the clinical practice,basic research,and drug development of UC-CRC.

Construction of miRNA-mRNA regulatory network and drug prediction for ulcerative colitis associated colorectal cancer

Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.

Colorectal cancer in inflammatory bowel disease:What is the real magnitude of the risk?

The association between inflammatory bowel disease(IBD) and colorectal cancer(CRC) has been recognised since 1925 and still accounts for 10%-15% of deaths in IBD.IBD-associated CRC(IBD-CRC) affects patients at a younger age than sporadic CRC.The prognosis for sporadic CRC and IBD-CRC is similar,with a 5-year survival of approximately 50%.Identifying at risk patients and implementing appropriate surveillance for these patients is central to managing the CRC risk in IBD.The increased risk of colorectal cancer in association with IBD is thought to be due to genetic and acquired factors.The link between inflammation and cancer is well recognised but the molecular biology,immune pathobiology and genetics of IBD-CRC are areas of much ongoing research.This review examines the literature relating to IBD-CRC,focusing on the incidence of IBD-CRC and examining potential risk factors including age at diagnosis,gender,duration and extent of colitis,severity of inflammation,family history of sporadic CRC and co-existent primary sclerosing cholangitis(PSC).Confirmed risk factors for IBD-CRC are duration,severity and extent of colitis,the presence of co-existent PSC and a family history of CRC.There is insufficient evidence currently to support an increased frequency of surveillance for patients diagnosed with IBD at a younger age.Evidence-based guidelines advise surveillance colonoscopy for patients with colitis 8 to 10 years after diagnosis,with the interval for further surveillance guided by risk factors(extent of disease,family history of CRC,post-inflammatory polyps,concomitant PSC,personal history of colonic dysplasia,colonic strictures).There is a move away from using random colonic biopsies towards targeted biopsies aimed at abnormal areas identified by newer colonoscopic techniques(narrow band imaging,chromoendoscopy,confocal microendoscopy).