Colorectal Neoplasia and Microbiota: Does Left Equal Right?
Ontology highlight
ABSTRACT: Many studies, including our own, have shown that colorectal cancer (CRC) is related to changes in the microbiome of the colon. However, there are limitations in most studies and questions remained unanswered. Some early data showing that the microbiome in the left vs right colon are different.
The aim of this study is to investigate the microbiome (including bacteriome, virome, and fungome) of adenoma/CRC comparing the left (distal to splenic flexure) vs right side (proximal to splenic flexure) of the colon.
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
Project description:Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). CRC is known to display glycosylation alterations. Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer, such as cell signaling and adhesion, and may can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples from patients with tumors in the right or left colon and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left side of the colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right- and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways, regardless of tumor location.
Project description:The degree of protection afforded by colonoscopy against proximal colorectal cancer (CRC) appears to be related to the quality of the procedure, and the incomplete removal of lesions has been shown to increase the subsequent risk of developing a colon cancer.
Some studies suggest that small polyps with advanced histology are more common in the right than in the left colon (right colon proximal to splenic flexure, left colon distal to the splenic flexure). The average size of polyps in the right colon with advanced pathology or containing adenocarcinoma was ≤9 mm, whereas in the left colon their average size was >9 mm, P<0.001. Inadequate prevention of right-sided CRC incidence and mortality may be due to right-sided polyps with advanced histology or that harbor malignancy. These presumptive precursors of cancer are smaller and possibly more easily obscured by residual feces, and more likely to be missed at colonoscopy.
Water-aided colonoscopy (WAC) can be subdivided broadly into two major categories: water immersion (WI), characterized by suction removal of the infused water predominantly during the withdrawal phase of colonoscopy, and water exchange (WE), characterized by suction removal of infused water predominantly during the insertion phase of colonoscopy.
In some reports WE appeared to be superior to both WI and air insufflation colonoscopy (AI) in terms of pain reduction and adenoma detection, particularly for <10 mm adenomas in the proximal colon.
In this multicenter, double-blinded randomized controlled trial (RCT) we test the hypothesis that that WE, compared to AI and WI, will enhance overall Adenoma Detection Rate (ADR) in CRC screening patients. Confirmation of the primary hypothesis will provide evidence that WE enhances the quality of screening colonoscopy.
We also hypothesize that WE may be more effective in detecting proximal colon adenomas than WI and AI, particularly <10 mm adenomas, thus increasing proximal colon ADR and proximal colon ADR <10 mm. Confirmation of secondary hypotheses will provide justification for further testing that WE may provide a strategy to improve prevention of colorectal cancer by increasing detection of adenomas in screening colonoscopy.
Unlike previous reports of single colonoscopist studies, the insertion and withdrawal phases of colonoscopy will be done by different investigators. The second investigator will be blinded to the method used to insert the instrument, thus eliminating possible bias about procedure related issues.
Several secondary outcomes will also be analysed.
Project description:In our study, we obtained paired normal left-sided and right-sided colon mucosa tissues by colonoscopy, and 9,642 individual cells were analyzed by single-cell RNA-seq, which aims to explore the differennces of cell component between the left and the right colon.
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and is a heterogeneous disease, with differences between cancer in the right colon, left colon, and rectum. In this study, plasma samples from CRC patients with varying stage (II or III), primary tumor location (right colon, left colon, or rectum) and survival (survived or died due to CRC) were studied with quantitative label-free proteomics using ultra-definition MSE. Patients were also divided into subgroups based on preoperative radiotherapy status and gender. Further analysis subsequently identified multiple plasma proteins whose expression differed depending on tumor stage, location, patient survival, preoperative radiotherapy status, or gender.
Project description:Interventions: Drug : 1. WLE-Fluorescence Group
?Insert colonoscopy with a transparent distal attachment under white light endoscopy (WLE).
?Intravenous administration of fluorescein sodium 1 ampule (10%, 5 mL) after cecal intubation
?WLE examination from cecum to hepatic flexure and record lesions detected.
?Insert colonoscopy under WLE up to cecum and then fluorescence endoscopic examination from cecum to hepatic flexure. Record and remove lesions detected.
?WLE examination from transverse colon to splenic flexure and record lesions detected.
?Insert colonoscopy under WLE up to hepatic flexure and then fluorescence endoscopic examination from transverse colon to splenic flexure. Record and remove lesions detected.
?WLE examination from descending colon to rectum and record lesions detected.
?Insert colonoscopy under WLE up to descending colon and then fluorescence endoscopic examination from descending colon to rectum. Record and remove lesions detected.
2. Fluorescence-WLE Group
?Insert colonoscopy with a transparent distal attachment under white light endoscopy (WLE).
?Intravenous administration of fluorescein sodium 1 ampule (10%, 5 mL) after cecal intubation
?Fluorescence endoscopic examination from cecum to hepatic flexure and record the lesions detected
?Insert colonoscopy under WLE up to cecum and then WLE examination from cecum to hepatic flexure. Record and remove the lesions detected.
?Fluorescence endoscopic examination from transverse colon to splenic flexure and record the lesions detected
?Insert colonoscopy under WLE up to hepatic flexure and then WLE examination from transverse colon to splenic flexure. Record and remove lesions detected.
?Fluorescence endoscopic examination from descending colon to r
Primary outcome(s): Number of fluorescence positive polyps
Primary Purpose : Diagnosis, Intervention Model : Cross-over, Blinding/Masking : Open, Allocation : RCT
Project description:Proximal Colon (i.e. proximal to hepatic flexure) versus Terminal ileum Transcriptomes (Affymetrix array U133A). All subjects were operated on for proximal-colon tumor (biopsies of proximal-colon normal mucosa were made at more than 5 cm from the site of the tumor).
Project description:The infrapyloric (No.206) and greater curvature (No.204) lymph node metastasis in adenocarcinoma located at hepatic flexure and right half of transverse colon has not been well discribed and analysed. The aim of this study is to assess the rate of this lymph node metastasis and to reveal its prognostic value for colon cancer located at hepatic flexure and right half of transverse colon. Meanwhile, we can evaluate the safety and feasibility of this extented lymphadenectomy in right hemi-colectomy.