Huanlong Qin

Association Between Vitamin D and Risk of Colorectal Cancer: A Systematic Review of Prospective Studies

PURPOSE To conduct a systematic review of prospective studies assessing the association of vitamin D intake or blood levels of 25-hydroxyvitamin D [25(OH)D] with the risk of colorectal cancer using meta-analysis. METHODS Relevant studies were identified by a search of MEDLINE and EMBASE databases before October 2010 with no restrictions. We included prospective studies that reported relative risk (RR) estimates with 95% CIs for the association between vitamin D intake or blood 25(OH)D levels and the risk of colorectal, colon, or rectal cancer. Approximately 1,000,000 participants from several countries were included in this analysis. RESULTS Nine studies on vitamin D intake and nine studies on blood 25(OH)D levels were included in the meta-analysis. The pooled RRs of colorectal cancer for the highest versus lowest categories of vitamin D intake and blood 25(OH)D levels were 0.88 (95% CI, 0.80 to 0.96) and 0.67 (95% CI, 0.54 to 0.80), respectively. There was no heterogeneity among studies of vitamin D intake (P = .19) or among studies of blood 25(OH)D levels (P = .96). A 10 ng/mL increment in blood 25(OH)D level conferred an RR of 0.74 (95% CI, 0.63 to 0.89). CONCLUSION Vitamin D intake and blood 25(OH)D levels were inversely associated with the risk of colorectal cancer in this meta-analysis.

Obesity and Risk of Colorectal Cancer: A Systematic Review of Prospective Studies

Background Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer (CRC). To conduct a systematic review of prospective studies assessing the association of obesity with the risk of CRC using meta-analysis. Methodology/Principal Findings Relevant studies were identified by a search of MEDLINE and EMBASE databases before January 2012, with no restrictions. We also reviewed reference lists from retrieved articles. We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between general obesity [measured using body mass index (BMI)] or central obesity [measured using waist circumference (WC)] and the risk of colorectal, colon, or rectal cancer. Approximately 9, 000, 000 participants from several countries were included in this analysis. 41 studies on general obesity and 13 studies on central obesity were included in the meta-analysis. The pooled RRs of CRC for the obese vs. normal category of BMI were 1.334 (95% CI, 1.253–1.420), and the highest vs. lowest category of WC were 1.455 (95% CI, 1.327–1.596). There was heterogeneity among studies of BMI (P<0.001) but not among studies of WC (P = 0.323). Conclusions Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.

miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer

Background MicroRNAs (miRNA) have potential as prognostic biomarkers and therapeutic targets in cancer. A study was undertaken to investigate the association between miRNA expression patterns and the prognosis and therapeutic outcome of colorectal cancer (CRC). Methods miRNA expression profiling in tumour, adenoma and normal colorectal tissues was performed to identify tumour-related miRNAs in the course of colorectal malignant changes. Quantitative reverse transcription PCR (qRT-PCR) assays were used to measure tumour-related miRNA and to assess its association with survival and response to adjuvant chemotherapy in 239 patients. In addition, to validate the findings, associations of the tumour-related miRNA with clinical characteristics of CRC were analysed in 185 patients by in situ hybridisation (ISH) analysis. Results Only one miR-150 was found to show a decrease in expression levels in the three tissue groups (normal, adenoma and cancer tissue) in parallel with increasing carcinogenesis of the colorectal tissue. In both ISH and qRT-PCR analysis, tumour tissue had reduced levels of miR-150 expression compared with paired non-cancerous tissue, which indicated that the levels of miR-150 expression were associated with CRC. Moreover, patients whose tumours had low miR-150 expression had shorter survival and a worse response to adjuvant chemotherapy than patients whose tumours had high miRNA expression. Conclusions The miR-150 expression status of patients with CRC is associated with survival and response to adjuvant chemotherapy. It is suggested that miR-150 should be considered as a potential biomarker associated with the prognosis and therapeutic outcome in CRC.

L. plantarum prevents Enteroinvasive Escherichia coli-induced tight junction proteins changes in intestinal epithelial cells

BackgroundIt is increasingly recognized that Lactobacillus plantarum (L. plantarum) has the ability to protect against Enteropathogenic Escherichia coli (EPEC)-induced damage of the epithelial monolayer barrier function by preventing changes in host cell morphology, attaching/effacing (A/E) lesion formation, monolayer resistance, and macromolecular permeability. However, the cellular mechanism involved in this protective effect still remained to be clarified.MethodsThis study was to investigate the effect of L. plantarum on the changes of Caco-2 cells responding to Enteroinvasive Escherichia coli (EIEC), the permeability of cell monolayer and the transmissivity of dextran, and the distribution and expression of the tight junction (TJ) proteins, such as Claudin-1, Occludin, JAM-1 and ZO-1 were examined when infected with EIEC or adhesived of L. plantarum after infection by confocal laser scanning microscopy (CLSM), immunohistochemistry and Western blotting, the cytoskeleton protein F-actin were observed with FITC-phalloidin.ResultsThis study demonstrated that the transepithelial electrical resistance (TER) step down and dextran integrated intensity (DII) step up with time after infected with EIEC, but after treating with L. plantarum, the changes of TER and DII were improved as compared with EIEC group. L. plantarum prevented the damage of expression and rearrangement of Claudin-1, Occludin, JAM-1 and ZO-1 proteins induced by EIEC, and could ameliorate the injury of cytoskeleton protein F-actin infected with EIEC.ConclusionL. plantarum exerted a protective effect against the damage to integrity of Caco-2 monolayer cells and the structure and distribution of TJ proteins by EIEC infection.

Microbiota disbiosis is associated with colorectal cancer

The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent non-cancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individuals differed significantly. Firmicutes and Fusobacteria were over-represented whereas Proteobacteria was under-represented in CRC patients. In addition, Lactococcus and Fusobacterium exhibited a relatively higher abundance while Pseudomonas and Escherichia-Shigella was reduced in cancerous tissues compared to adjacent non-cancerous tissues. Meanwhile, the overall microbial structures of proximal and distal colon cancerous tissues were similar; but certain potential pro-oncogenic pathogens were different. These results suggested that the mucosa-associated microbiota is dynamically associated with CRC, which may provide evidences for microbiota-associated diagnostic, prognostic, preventive, and therapeutic strategies for CRC.

Candidate microRNA biomarkers in human colorectal cancer: Systematic review profiling studies and experimental validation†

Colorectal cancer (CRC) is a major cause of cancer mortality worldwide. There is an urgent need to search for specific and sensitive biomarkers for early diagnosis of CRC. We carried out a comprehensive systematic review of published studies that compared the miRNA expression profiles between CRC tissue and paired neighboring noncancerous colorectal tissue to determine candidate miRNA biomarkers for CRC. A miRNA ranking system that takes the number of comparisons in agreement, total study sizes and direction of differential expression into the consideration was devised and used. One of the most up‐regulated miRNAs, miRNA‐106a, was consistently reported to be differentially expressed in six studies and the five most down‐regulated miRNAs, miR‐30a‐3p, miR‐139, miR‐145, miR‐125a and miR‐133a, were consistently reported to be differentially expressed in four studies. Moreover, we further validated five miRNAs in a clinical setting using qRT‐PCR, which demonstrated that miR‐106a expression was increased, whereas the expression of miR‐30a‐3p, miR‐145, miR‐125a and miR‐133a was decreased in the CRC tissues. Therefore, these miRNAs may be the candidates to develop a panel of biomarkers with sufficient sensitivity and specificity for the diagnosis of CRC in a clinical setting.

The role of gut microbiota in the pathogenesis of colorectal cancer

The human gastrointestinal tract harbors a complex and abundant microbial community that can reach levels as high as 1013–1014 microorganisms in the colon. These microorganisms are essential to a host’s well-being in terms of nutrition and mucosa immunity. However, numerous studies have also implicated members of the colonic microbiota in the development of colorectal cancer (CRC). While CRC involves a genetic component where damaged DNA and genetic instability initiates a malignant transformation, environmental factors can also contribute to the onset of CRC. Furthermore, considering the constant exposure of the colonic mucosa to the microbiome and/or its metabolites, the mucosa has long been proposed to contribute to colon tumorigenesis. However, the mechanistic details of these associations remain unknown. Fortunately, due to technical and conceptual advances, progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of human gut microbiota have been made, thereby elucidating its role in human health and disease. Furthermore, the use of experimental animal models and clinical/epidemiological studies of environmental etiological factors has identified a correlation between gut microbiota composition and gastrointestinal cancers. Bacteria continuously stimulate activated immunity in the gut mucosa and also contribute to the metabolism of bile and food components. However, the highest levels of carcinogen production are also associated with gut anaerobic bacteria and can be lowered with live lactobacilli supplements. In this review, evidence regarding the relationship between microbiota and the development of CRC will be discussed, as well as the role for microbial manipulation in affecting disease development.

Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery – a double-blind study

Aliment Pharmacol Ther 2011; 33: 50–63

Randomized clinical trial to compare the effects of preoperative oral carbohydrate versus placebo on insulin resistance after colorectal surgery

Preoperative oral carbohydrate (OCH) reduces postoperative insulin resistance (PIR). This randomized trial investigated whether this effect is related to insulin‐induced activation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (PKB) signalling pathway.

Proteomics Identification of Desmin as a Potential Oncofetal Diagnostic and Prognostic Biomarker in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the oncofetal proteins involved in CRC carcinogenesis, differentially expressed proteins among fetal colorectal tissues, CRC, and the paired tumor-adjacent normal colorectal tissues were investigated by a two-dimensional gel electrophoresis and MALDI-TOF/TOF-based proteomics approach. 42 protein spots were differentially expressed among these tissues, and 22 proteins were identified by MS analysis. Desmin and zinc finger protein 829 were found to be elevated in CRC tissue and fetal colorectal tissue compared with normal colorectal tissue. The elevated expression of desmin in CRC tissue and different developmental stages of fetus colon was confirmed by RT-PCR and Western blot analysis. Immunohistochemical analysis showed that the elevated expression of desmin was correlated with the severity and differentiation of CRC and decreased survival rate of CRC patients. Finally by developing a highly sensitive immunoassay, desmin could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We propose that desmin be considered a potential oncofetal serum tumor marker for CRC that may have significance in the detection of patients with CRC.