Colorectal cancer is one of the most common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. As miR-7, a putative tumor-suppressor, ...regulates the expression of several important drivers of colorectal cancer, we analyzed the clinical significance of ciRS-7 in colorectal cancer patients.
Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary colorectal cancer tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (
= 165), and evaluated the effect of ciRS-7 on miR-7, and its target genes EGFR and RAF1. Functional analyses were performed in cell lines and an animal model to support clinical findings.
Our data revealed that ciRS-7 was significantly upregulated in colorectal cancer tissues compared with matched normal mucosae (
= 0.0018), and its overexpression was associated with poor patient survival (
= 0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (
= 0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes.
CiRS-7 is a promising prognostic biomarker in colorectal cancer patients and may serve as a therapeutic target for reducing EGFR-RAF1 activity in colorectal cancer patients.
.
The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA ...gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC.
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.
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).
Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Emerging evidence suggests a potential relationship between gut microbiota and the host response to chemotherapeutic drugs including 5-fluorouracil (5-Fu). Fusobacterium nucleatum (Fn) has been ...linked to the initiation and progression of colorectal cancer (CRC). Unfortunately, little was known about the relationship between Fn infection and chemotherapeutic efficacy. Here, we investigate the potential relationship between Fn infection and chemotherapeutic efficacy of 5-Fu in CRC.
Differentially expressed genes of CRC cell lines induced by Fn infection were analyzed based on a whole genome microarray analysis Then, we explored the relationship between upregulation of BIRC3 induced by Fn infection and chemoresistance to 5-Fu in vitro and in vivo. Furthermore, we dissected the mechanisms involved in Fn-induced BIRC3 expression. Finally, we investigated the clinical relevance of Fn infection, BIRC3 protein expression and chemoresistance to 5-Fu treatment in CRC patients.
BIRC3 was the most upregulated gene induced by Fn infection via the TLR4/NF-κB pathway in CRC cells; Fn infection reduced the chemosensitivity of CRC cells to 5-Fu through upregulation of BIRC3 in vitro and in vivo. High Fn abundance correlated with chemoresistance in advanced CRC patients who received standard 5-Fu-based adjuvant chemotherapy after radical surgery.
Our evidence suggests that Fn and BIRC3 may serve as promising therapeutic targets for reducing chemoresistance to 5-Fu treatment in advanced CRC.
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).
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.
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.
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.
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.
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.
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).
Vitamin D intake and blood 25(OH)D levels were inversely associated with the risk of colorectal cancer in this meta-analysis.
Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet ...on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt
CD3
group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a ...kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy.
Emerging research has revealed regulation of colorectal cancer metabolism by bacteria.
(
) plays a crucial role in the development of colorectal cancer, however, whether
infection modifies metabolism ...in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells
and
by regulating the epithelial-mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal
and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high
levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover,
was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that
promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for
-infected patients with colorectal cancer. SIGNIFICANCE: This study uncovers a mechanism by which
regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13-EpOME axis in
-infected patients.
Background
Robotic colorectal surgery may solve some of the problems inherent to conventional laparoscopic surgery (CLS). We sought to evaluate the advantages of robot-assisted laparoscopic surgery ...(RALS) using the da Vinci Surgical System over CLS in patients with benign and malignant colorectal diseases.
Methods
PubMed and Embase databases were searched for relevant studies published before July 2011. Studies clearly documenting a comparison of RALS with CLS for benign and malignant colorectal diseases were selected. Operative and postoperative measures, resection margins, complications, and related outcomes were evaluated. Weighted mean differences, relative risks, and hazard ratios were calculated using a random-effects model.
Results
The meta-analysis included 16 studies comparing RALS and CLS in patients with colorectal diseases and 7 studies in rectal cancer. RALS was associated with lower estimated blood loss in colorectal diseases (
P
= 0.04) and rectal cancer (
P
< 0.001) and lower rates of intraoperative conversion in colorectal diseases (
P
= 0.03) and rectal cancer (
P
< 0.001) than CLS. In patients with colorectal diseases, however, operating time (
P
< 0.001) and total hospitalization cost (
P
= 0.06) were higher for RALS than for CLS.
Conclusions
RALS was associated with reduced estimated blood loss and a lower intraoperative conversion rate than CLS, with no differences in complication rates and surrogate markers of successful surgery. Robotic colorectal surgery is a promising tool, especially for patients with rectal cancer.
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