• Bcl‐2
• autophagy
• colorectal cancer
• hsa_circ_0000231
• invasion
• miR‐140‐3p
• proliferation

• Humans
• MicroRNAs/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• RNA, Circular/genetics
• Cell Proliferation/genetics
• Proto-Oncogene Proteins c-bcl-2/genetics
• Proto-Oncogene Proteins c-bcl-2/metabolism
• Autophagy/genetics
• Gene Expression Regulation, Neoplastic
• Cell Movement/genetics
• Cell Line, Tumor
• Neoplasm Invasiveness/genetics
• Male
• Female
• Middle Aged
• Apoptosis

• The present study was supported by grants from the National Natural Science Foundation of China (grant nos. 81871962 and 81972240).

• Endoscopic resection (polypectomy, ESD, EMRc, ...)
• Endoscopy Lower GI Tract
• Polyps / adenomas / ...
• Tissue diagnosis

Although substantial evidence supports the advantages of cold snare polypectomy (CSP) in terms of polypectomy efficacy and reduced postoperative adverse events, few studies have examined the cost differences between CSP and traditional endoscopic mucosal resection (EMR) for the treatment of intestinal polyps.

To compare the efficacy-cost of EMR and CSP in the treatment of intestinal polyps.

A total of 100 patients with intestinal polyps were included in the retrospective data of our hospital from April 2022 to May 2023. According to the treatment methods, they were divided into EMR (n = 46) group and CSP (n = 54) group. The baseline data of the two groups were balanced by 1:1 propensity score matching (PSM), and the cost-effectiveness analysis was performed on the two groups after matching. The recurrence rate of the two groups of patients was followed up for 1 year, and they were divided into recurrence group and non-recurrence group according to whether they recurred. Multivariate logistic regression analysis was used to screen out the influencing factors affecting the recurrence of intestinal polyps after endoscopic resection.

Significant disparities were observed in the number of polyps and smoking background between the two groups before PSM (P < 0.05). Following PSM, the number of polyps and smoking history were well balanced between the EMR and CSP groups. The direct cost incurred by the CSP group was markedly higher than that incurred by the EMR group. Concurrently, the cost-effectiveness ratio in the CSP group was substantially reduced when juxtaposed with that in the EMR group (P < 0.05). Upon completion of the 1-year follow-up, the rate of recurrence after endoscopic intestinal polypectomy was 38.00%. Multivariate methods revealed that age ≥ 60 years, male sex, number of polyps ≥ 3, and pathological type of adenoma were risk factors for recurrence after endoscopic intestinal polypectomy (all P < 0.05).

CSP was more cost-effective for the treatment of intestinal polyps. An age ≥ 60 years, male sex, having a number of polyps ≥ 3, and pathological type of adenoma are independent influencing factors for recurrence.

• Propensity score matching method
• Endoscopic mucosal resection
• Cold snare polypectomy
• Intestinal polyps
• Curative effect
• Cost analysis

• Hippo-YAP
• Wnt pathway
• biomarker
• colorectal adenoma
• oncogene

• Humans
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Adenoma/pathology
• Adenoma/genetics
• Adenoma/metabolism
• Male
• Female
• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Middle Aged
• YAP-Signaling Proteins
• beta Catenin/metabolism
• beta Catenin/genetics
• Transcription Factors/genetics
• Aged
• Biomarkers, Tumor/genetics
• Gene Expression Regulation, Neoplastic
• Mutation
• Adenomatous Polyposis Coli Protein/genetics
• Carcinogenesis/genetics
• Phosphoproteins/genetics
• Phosphoproteins/metabolism

• Vanderbilt University Medical Center's Digestive Disease Research Center
• Biospecimen and Survey Shared Resource at Vanderbilt
• R01 CA097386 NCI NIH HHS
• P30CA68485 NIH HHS
• P30DK0584 NIH HHS
• P50CA950103 NCI NIH HHS
• Tissue Morphology Core Services
• VR51499 Vanderbilt Institute for Clinical and Translational Research
• National Cancer Institute
• National Institutes of Health
• Vanderbilt University Medical Center’s Digestive Disease Research Center
• NIH

• TRPM8 receptor
• ccnb1
• colorectal cancer
• inorganic polyphosphate
• organoids
• proliferation

• Ricerca Corrente 2024 Ministero della Salute

• bilateral
• colonoscopy
• colorectal polypectomy
• nasopharyngeal airway
• obese patients
• sedation anesthesia

• had no role in the design of the study and collection, analysis, and interpretation of data and in writing

• colorectal adenocarcinoma
• colorectal adenoma
• differentially expressed genes
• immune infiltration
• prognosis
• progress

Colorectal cancer remains a considerable challenge in healthcare nowadays. Approximately 60%-80% of colorectal cancer is caused by intestinal polyps, and resection of intestinal polyps has been proved to reduce the incidence of colorectal cancer. The vast majority of intestinal polyps can be found during colonoscopy and removed endoscopically. Therefore, more attention has been paid to the development of endoscopic resection of intestinal polyps. In this study, we compared the efficacy and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP).

To investigate the efficacy and safety of CSP and HSP for colorectal polyps.

Between January and December 2020, 301 patients with colorectal polyps 4-9 mm in diameter were treated with endoscopic therapy in our hospital, and were divided into the CSP group (n = 154) and HSP group (n = 147). The operating time, incidence of bleeding and perforation, use of titanium clips, and complete resection rate were compared between the two groups.

We included 249 patients (301 polyps). No differences in gender, age, and polyp size, location, shape and type were observed between the CSP and HSP groups, and the resection rates in these two groups were 93.4% and 94.5%, respectively, with no significant difference. The use of titanium clips was 15.6% and 95.9%, the operating time was 3.2 ± 0.5 min and 5.6 ± 0.8 min, the delayed bleeding rate was 0% and 2.0%, and delayed perforation was 0% and 0.7%, in the CSP and HSP groups, respectively.

For sessile colorectal polyps < 10 mm, CSP had the same resection rate of impaired tissue integrity as traditional HSP had. The rate of complications was lower in the CSP group. CSP is a safe and effective method for polypectomy.

• Colorectal polyps
• Cold snare polypectomy
• Hot snare polypectomy
• Complete polypectomy rate
• Immediate bleeding
• Delayed bleeding

• Cold Snare Polypectomy
• Colorectal Polyps
• Incomplete Resection Rate
• Sessile Serrated Lesion

• CUL4B
• Colorectal cancer
• Invasion
• Proliferation
• p53 signaling pathway

This study aimed to evaluate the role and the underlying mechanisms of Forkhead box A1 (encoded by FOXA1) in colon cancer.

We analyzed FOXA1 mRNA and protein expression in colon cancer tissues and cell lines. We also silenced FOXA1 expression in HCT116 and SW480 cells to evaluate the effects on cell proliferation, cell cycle, migration, and invasion by using MTT, colony formation, flow cytometry, and the Transwell assay, respectively.

FOXA1 immunostaining was higher in colon cancer tissues than adjacent healthy tissues. FOXA1 mRNA and protein expression was significantly increased in human colon cancer cells compared with a normal colonic cell line. FOXA1 expression was also significantly higher in colorectal cancer tissues from TCGA data sets and was associated with worse prognosis in the R2 database. FOXA1 expression was negatively correlated with the extent of its methylation, and its knockdown reduced proliferation, migration, and invasion, and induced G2/M phase arrest in HCT116 and SW480 cells by suppressing the phosphatase and tensin homolog/Akt signaling pathway and inhibiting epithelial–mesenchymal transition.

FOXA1 may act as an oncogene in colon cancer tumorigenesis and development.

• Colon cancer
• Forkhead box A1
• invasion
• migration
• phosphatase and tensin homolog/Akt signaling pathway
• proliferation

Colorectal cancer (CRC) is one of the most common types of human cancer. However, there is still an urgent need to identify novel treatment strategies for CRC. The present study aimed to validate the potential antitumor effects of polyphyllin VII in CRC. The present study revealed that polyphyllin VII could significantly inhibit CRC proliferation and induce cell cycle arrest and apoptosis. Moreover, the anti-metastatic effect of polyphyllin VII in CRC cells was implicated. Microarray analysis identified that polyphyllin VII could affect multiple protein coding genes and non-coding RNAs. Bioinformatics analysis revealed that polyphyllin VII regulated multiple pathways in CRC, including ‘ER to Golgi vesicle-mediated transport’, ‘response to cAMP’, ‘Ras protein signal transduction’, ‘metabolic pathways’, ‘MAPK signaling pathway’ and ‘cell cycle’. Protein-Protein Interaction network analysis identified a series of key polyphyllin VII-regulating genes in CRC, including ribonucleoside-diphosphate reductase subunit M2, structural maintenance of chromosomes protein 4 and DNA replication licensing factor MCM4. Finally, the present results demonstrated that these key polyphyllin VII-regulating genes were dysregulated in CRC. Taken together, these results indicated that polyphyllin VII could be a novel antitumor drug for the treatment of CRC.

• cell cycle
• colorectal cancer
• migration
• polyphyllin VII
• proliferation

The morbidity and mortality of colorectal cancer (CRC) remained to be very high worldwide. Recently, circRNAs had been revealed to have a crucial role in cancer prognosis and progression. Numerous researches have shown that RNA sequencing technology and in silico method were widely used to identify pathogenic mechanisms and uncover promising targets for diagnosis and therapy. In this study, these methods were analyzed to obtain differentially expressed circRNAs (DECs). We identified upregulated 316 circRNAs and reduced 76 circRNAs in CRC samples, in comparison with those in normal tissues. In addition, a competitive endogenous network of circRNA-miRNA-mRNA was established to predict the mechanisms of circRNAs. Bioinformatics analysis revealed that these circRNAs participated in metabolism regulation and cell cycle progression. Of note, we observed the hub genes and miRNAs in this ceRNA network were associated with the survival time in CRC. We think this study could provide potential prognostic biomarkers and targets for CRC.

The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain‐ and loss‐of‐function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR‐212‐5p was identified to directly target the SIRT2 3′‐untranslated region (3′‐UTR), leading to SIRT2 down‐regulation. The ectopic expression of SIRT2 reverses the effect of miR‐212‐5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR‐212‐5p and SIRT2 expression. High miR‐212‐5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR‐212‐5p, acts as a tumour suppressor in CRC and that the miR‐212‐5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.

• colorectal cancer
• metastasis
• miR-212-5p
• prognosis
• sirtuin 2
• tumorigenesis

• Ago2
• DGCR8
• DROSHA
• E-cadherin
• GW182
• PLEKHA7
• RNA interference
• colorectal
• p120 catenin
• tumor suppressor

• Adherens Junctions/metabolism
• Animals
• Carcinogenesis/metabolism
• Cell Line
• Cell Proliferation/physiology
• Colon/metabolism
• Colonic Neoplasms/metabolism
• Cytoplasm/metabolism
• Epithelial Cells/metabolism
• Female
• Humans
• Intestinal Mucosa/metabolism
• Male
• Mice
• MicroRNAs/metabolism
• RNA Interference/physiology
• RNA-Binding Proteins/metabolism
• Ribonuclease III/metabolism

• P30 DK123704 NIDDK NIH HHS
• P20 GM103499 NIGMS NIH HHS
• P30 CA138313 NCI NIH HHS
• P20 GM130457 NIGMS NIH HHS
• UL1 TR001450 NCATS NIH HHS
• R50 CA211529 NCI NIH HHS
• TL1 TR001451 NCATS NIH HHS

High‐fat diet (HFD) is a well‐known risk factor for gut microbiota dysbiosis and colorectal cancer (CRC). However, evidence relating HFD, gut microbiota and carcinogenesis is limited. Our study aimed to demonstrate that HFD‐induced gut dysbiosis promoted intestinal adenoma‐adenocarcinoma sequence. In clinical study, we found that HFD increased the incidence of advanced colorectal neoplasia (AN). The expression of monocyte chemoattractant protein 1 (MCP‐1), CC chemokine receptor 2 (CCR2) and CD163 in CRC patients with HFD was significantly higher than that in CRC patients with normal diet. When it comes to the Apc^min/+ mice, HFD consumption could induce gut dysbiosis and promote intestinal carcinogenesis, accompanying with activation of MCP‐1/CCR2 axis that recruited and polarized M2 tumour‐associated macrophages. Interestingly, transfer of faecal microbiota from HFD‐fed mice to another batch of Apc^min/+ mice in the absence of HFD could also enhance carcinogenesis without significant body weight gain and induced MCP‐1/CCR2 axis activation. HFD‐induced dysbiosis could also be transmitted. Meanwhile, antibiotics cocktail treatment was sufficient to inhibit HFD‐induced carcinogenesis, indicating the vital role of dysbiosis in cancer development. Conclusively, these data indicated that HFD‐induced dysbiosis accelerated intestinal adenoma‐adenocarcinoma sequence through activation of MCP‐1/CCR2 axis, which would provide new insight into better understanding of the mechanisms and prevention for HFD‐related CRC.

• MCP-1/CCR2 axis
• gut microbiota
• high-fat diet
• intestinal carcinogenesis
• tumour-associated macrophages

• Chinese medicine
• adenomatous polyps
• biomarkers
• metabolomics
• ultra-performance liquid chromatography-mass spectrometry
• yang-deficiency constitution

Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.

The Apc^min/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.

The Apc^min/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.

Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apc^min/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted.

The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.

• Apc(min/+) mice
• Colorectal cancer
• Fecal microbiota transplantation
• Gut microbiota
• Wnt signalling pathway

Effective therapies are limited for pancreatic cancer, particularly for those with distant tumour metastases. Therefore, more individualised drug screening is urgently required. Next-generation sequencing (NGS) is a powerful tool to investigate the genomic landscape of patients and the mechanism of drug response, which may provide a broader vision for potential clinical drug screening. Patient-derived xenograft (PDX) models may have a significant advantage in predicting clinical treatment response. In our previous study, a PDX of pancreatic cancer bone metastasis was established, and NGS was conducted to investigate the molecular information. In the present study, these data were further analysed and fibroblast growth factor receptor 1 (FGFR1) amplification was identified in a panel of 416 cancer-associated genes. Thus, AZD4547, an inhibitor against FGFR, was selected as a potential therapy, and was evaluated using the PDX model. AZD4547 was shown to exhibit antitumor activity by reducing the expression of FGFR1 and its targets. The present study also demonstrated the high potential of the novel NGS/PDX-based drug screening platform to improve individualised cancer treatment.

• fibroblast growth factor receptor
• next-generation sequencing
• pancreatic cancer with bone metastasis
• patient-derived xenograft model

• Rab3D
• colorectal cancer
• miR-761
• migration
• proliferation

• Activator protein 1 (AP-1)
• Basic leucine zipper transcriptional factor ATF-like 3 (BATF3)
• Colorectal cancer (CRC)
• microRNA-760 (miR-760)

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Female
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/metabolism
• Middle Aged
• Signal Transduction
• Transcription Factor AP-1/metabolism
• Transfection

• 201501004 the Ministry of Public Health

• CNV
• LOH
• colorectal cancer
• genetic aberrations
• neoplastic transformation

MicroRNAs (miRNAs/miRs) have been investigated as diagnostic and prognostic biomarkers for cancer; however, the significance of miRNAs in colorectal cancer (CRC) remains to be elucidated. The aim of the present study was to determine the genetic profiles of CRC tissue, and screen for miRNAs implicated in CRC cell proliferation and migration. RNA sequencing of 10 paired specimens was performed to for screen genes that were upregulated or downregulated in CRC. miRNA expression in CRC specimens and cell lines was confirmed using qPCR analysis. The significance of indicated miRNAs in CRC cell proliferation and migration was evaluated using MTT and scratch wound-healing assays. Online computational prediction, isobaric tags for relative and absolute quantification analysis and a luciferase reporter assay were applied to determine candidate targeted genes for the miRNAs. RNA-seq data revealed miR-1914 as the most prominent miRNA in CRC specimens. qPCR analysis also suggested that the expression of miR-1914, as well as its counterpart miR-647 were elevated in CRC specimens and cell lines. Suppression of miR-647/1914 using small interfering RNAs inhibited CRC SW480 and SW620 cell proliferation, and migration. Nuclear factor I/X (NFIX) was demonstrated to be a candidate for miR-647/1914 and mediated the oncogenic activity of miR-647/1914. In all, miR-647 and miR-1914 were demonstrated to promote the proliferation and migration of CRC cells by directly targeting NFIX. Therapeutic delivery of siRNAs targeting miR-647/1914 and overexpression of NFIX may be feasible approaches for CRC treatment.

Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free.

Tissues were identified as cancer-adjacent polyp (CAP)—residual adenoma contiguous with cancer—and cancer-free polyp (CFP)—adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients.

The mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04–1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01.

Adenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management.