Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, primarily due to liver metastasis. This study explores the role of centromere protein N (CENP-N) in mediating the methylation of septin 9 (SEPT9) and its subsequent effects on aerobic glycolysis and liver metastasis in CRC. We employed in vitro and in vivo experiments, including single-cell RNA sequencing, methylation-specific PCR (MSP), ChIP assays, and various functional assays to assess the impact of CENP-N and SEPT9 on CRC cell proliferation, migration, invasion, and metabolic reprogramming. Our data reveal that CENP-N directly interacts with SEPT9, enhancing its methylation at specific lysine residues. This modification significantly upregulates key glycolytic enzymes, thereby promoting aerobic glycolysis, CRC cell proliferation, and migration. In vivo studies further demonstrate that the CENP-N/SEPT9 axis facilitates liver metastasis of CRC, as confirmed by fluorescence imaging and histological analysis. This study identifies a novel pathway where CENP-N-mediated methylation of SEPT9 drives metabolic reprogramming and metastasis in CRC. These findings suggest potential therapeutic targets for inhibiting CRC progression and liver metastasis, offering new insights into CRC pathogenesis.

Colorectal cancer (CRC) is a global health concern, ranking among the leading causes of cancer-related mortality. This review critically evaluates the role of liquid biopsy in detecting minimal residual disease (MRD) in CRC. The increasing incidence, particularly in China, highlights the urgency of innovative approaches for early prediction of recurrence and metastasis. The importance of MRD should be underscored as residual tumor cells post-treatment significantly impact patient prognosis. Liquid biopsy methods, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and circulating tumor RNA, are dissected for their potential in identifying molecular markers associated with CRC. The focus on ctDNA highlights its non-invasive nature, real-time monitoring capabilities, and superiority over traditional detection methods in terms of sensitivity and timeliness. The review also delves into the limitations, such as clonal hematopoiesis and the critical consideration of optimal timing for postoperative ctDNA detection. In conclusion, the review highlights the significant potential of liquid biopsy, particularly ctDNA, as a dynamic and non-invasive tool for MRD detection in CRC. By complementing traditional methods, liquid biopsy contributes to precision in tumor research and personalized treatment. These advancements offer promising avenues for improving CRC patient prognosis and tailoring individualized treatment strategies.

BackgroundColorectal cancer (CRC) is one of the most common tumors worldwide, with rising numbers of elderly patients affected. Nutritional status significantly influences tumor prognosis. We aimed to investigate the association of subcutaneous and visceral adipose tissue and skeletal muscle mass with the prognosis of the oldest-old patients with CRC, after surgery.PatientsWe retrospectively reviewed 210 patients >75 years who underwent surgical treatment at the Department of Gastrointestinal Surgery, Beijing Hospital, between December 2010 and December 2020.MaterialsSubcutaneous adipose, visceral adipose, and skeletal muscle areas were measured using BMI_CT. The cut-off values of the CT measurements were then confirmed using receiver operating characteristic (ROC) curve analysis.ResultsSubcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and total adipose tissue index (TATI) were significantly associated with sex and BMI. Notably, the oldest-old CRC patients with high SATI, VATI, and TATI scores exhibited significantly higher rates of wound complications and reduced postoperative hospitalization durations. Intriguingly, patients with high VATI and TATI demonstrated significantly better 5-year Overall survival (OS), Cancer-specific survival (CSS), and Disease-free survival (DFS) than patients in the other groups. Similar results were observed in patients with a high visceral-to-subcutaneous fat ratio (VSR) and skeletal muscle index (SMI) scores.ConclusionSignificantly improving skeletal muscle content while concurrently managing the total adipose content, especially visceral adipose tissue, may aid in extending the survival time of oldest-old patients with CRC after surgery.

Peritoneal adhesions are a common and unsolvable problem in clinical practice. Their occurrence is related to many factors such as surgery and radiotherapy. The complications associated with peritoneal adhesions affect the quality of life. This article combines the literature to discuss the etiology, mechanism, diagnosis and treatment of peritoneal adhesions, hoping to reduce the occurrence of iatrogenic peritoneal adhesions and provide clinicians with reasonable and effective diagnosis and treatment strategies.

The advent of immunotherapy and the development of immune checkpoint inhibitors (ICIs) are changing the way we think about cancer treatment. ICIs have shown clinical benefits in a variety of tumor types, and ICI-based immunotherapy has shown effective clinical outcomes in immunologically "hot" tumors. However, for immunologically "cold" tumors such as colorectal cancer (CRC), only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates. In this review, we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC, and summarize the treatment strategies and challenges of immunotherapy for cold CRC. We also explain the mechanism, biology, and role of immunotherapy for cold CRC, which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.

Objective:To explore the correlation between age and treatment strategies and prognosis of metastatic colorectal cancer.Methods:A total of 43 977 patients with mCRC were identified from the National Cancer Database (NCDB) spanning ten years (2004~2014). Patients were classified into three age groups: 18~49, 50~75, and >75 years old. Percentages of patients within each treatment category were described, including primary tumor resection (PTR) only, chemotherapy only, and PTR plus chemotherapy. After adjusting for demographic and clinical factors, restricted mean survival time (RMST) was calculated and compared between different age and treatment groups.Results:The majority (61.8%) of patients in the 18~49 age group received PTR plus chemotherapy; about half (53.3%) of the patients in the 50~75 age group and about one third (34.7%) in the >75 age group received PTR plus chemotherapy. There was a decreasing trend in the PTR plus chemotherapy group and an increasing trend in the chemotherapy only group for mCRC patients over the study time period in all age groups. PTR plus chemotherapy demonstrated the most favorable survival rate in all age groups compared to other treatments. Chemotherapy only was associated with significantly higher survival time compared to PTR, except for patients in the ages 18~49 group. Among patients who had PTR plus chemotherapy treatment, peri-operative chemotherapy was associated with the longest survival rate among patients in the ages 18~49 and 50~75 groups, but not in the >75 group, compared to other treatments.Conclusion:A decreasing trend of PTR plus chemotherapy was observed among mCRC patients between 2004~2014, though it showed the most survival benefit in all age groups. The benefits of specific multimodality treatment vary by age group.

Purpose In recent years, natural orifice specimen extraction surgery (NOSES) has gained widespread attention as an alternative approach. Although the safety and feasibility of NOSES have been well documented, many questions remain open for discussion. The aim of this guideline is to provide more evidence for the promotion of NOSES. Methods This guideline has been prepared by the CACA Committee of Colorectal Cancer Society and the International NOSES Alliance, based on the latest evidence. Results The guideline on NOSES for colorectal cancer include the definition, classification, technology requirement, indications, technical difficulties and clinical research. Conclusion The guideline provides a full introduction of the theoretical and technical aspects of NOSES for colorectal cancer which will beneficial to development of NOSES.

[Objectives] To investigate the feasibility of extracting specimens from the preventive ileostomy site during laparoscopic low anterior resection for rectal cancer and its impact on ileostomy closure. [Methods] A retrospective analysis was conducted on the clinical data of 223 patients who underwent laparoscopic low anterior resection of rectal cancer combined with preventive ileostomy in Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from September 2015 to September 2019. Patients were divided into two groups based on whether specimens were extracted from the preventive ileostomy site: the ileostomy site extraction group (n＝114) and the non-ileostomy site extraction group (n＝109). The surgical indicators, wound and stoma-related complications, stoma closure surgery-related indicators, and stoma closure interval time were analyzed. [Results] Compared with the non-ileostomy site extraction group, the ileostomy site extraction group had a shorter operation time[169.0 (136.0，207.8) min vs. 211 (179，250) min，Z＝-5.755，P<0.001] and less intraoperative blood loss [30 (20，50) mL vs.50 (50，100) mL，Z＝-5.382，P<0.001]. In the non-ileostomy site extraction group, 4 patients (3.7%) with postoperative abdominal auxiliary incision bleeding, 2 patients (1.8%) with incision infection, and 1 patient (0.9%) with incisional hernia. In the ileostomy site extraction group, there were no abdominal auxiliary incisions or incision-related complications. The total incidence of incision-related complications was significantly different between the two groups (χ2＝7.558，P＝0.006). In the non-ileostomy site extraction group, 40 patients (36.7%) developed stoma-related complications, including 8 patients with stoma parastomal hernia (7.3%), 1 patient with prolapse (0.9%), 1 patient with ostomy retraction (0.9%), 1 patient with stricture (0.9%), 3 patients with bleeding (2.8%), and 1 patient with granuloma (0.9%), 17 patients with stoma peristomal dermatitis (15.6%), 4 patients with true skin ulceration (3.7%), and 4 with superficial mucocutaneous separation (3.7%). In the ileostomy site extraction group, 31 patients (27.2%) developed stoma-related complications, including 5 patients with stoma parastomal hernia (4.4%), 1 patient with stoma retraction (0.9%), 1 patient with bleeding (0.9%), 21 patients with stoma peristomal dermatitis (18.4%), and 3 patients with true skin ulceration (2.6%). There was no significant difference in the total incidence of stoma-related complications between the two groups (χ2＝2.319，P＝0.128). In the non-ileostomy site extraction group, 102 patients (93.6%) underwent ileostomy closure surgery, while in the ileostomy site extraction group, 102 patients (89.5%) underwent ileostomy closure surgery. There was no significant difference in the ileostomy closure rate between the two groups (χ2＝1.204，P＝0.272). Compared with the non-ileostomy site extraction group, the interval time of the ileostomy site extraction group from surgery to ileostomy closure was shorter [217 (147.5，289.5) min vs. 256.5 (193.8，371.0) min, Z＝-3.595, P<0.001], the surgical time was shorter [（80.8±25.3）min vs. （95.7±30.4）min，t＝14.902，P<0.001], and the intraoperative blood loss was less [20(10，20) mL vs. 30(20，50) mL，Z＝-4.927，P<0.001]. Optimal scale regression analysis showed that the site of specimen collection (P＝0.014), neoadjuvant chemotherapy (P＝0.037), adjuvant chemotherapy (P＝0.044), and postoperative complications (P＝0.018) were independent factors affecting the interval time of ileostomy closure. [Conclusion] Preventive ileostomy for specimens extracted during laparoscopic low anterior resection can shorten surgical time and interval time from surgery to ileostomy closure, reduce intraoperative blood loss and incision-related complications without increasing stoma-related complications, proving to be safe and feasible. In addition, the site of specimen collection, neoadjuvant chemotherapy, adjuvant chemotherapy, and postoperative complications are independent factors affecting the interval time from surgery to ileostomy closure.

Colorectal cancer (CRC) is the second most common cause of cancer-related death among both men and women worldwide and the third most common cancer overall. About 20% of patients diagnosed with CRC were discovered to have distant metastatic lesions, the majority of which were located in the liver. For the optimum treatment of CRC patients with hepatic metastases, interventional radiologists, medical oncologists, and surgeons must all collaborate. The surgical excision of the primary tumor is an important part of CRC treatment since it has been found to be curative in cases of CRC with minimal metastases. However, given the evidence to date was gathered from retrospective data, there is still controversy over the effectiveness of primary tumor resection (PTR) in improving the median overall survival (OS) and quality of life. Patients who have hepatic metastases make up a very tiny fraction of those who are candidates for resection. With a focus on the PTR, this minireview attempted to review the current advancements in the treatment options for hepatic colorectal metastatic illness. This evaluation also included information on PTR's risks when performed on individuals with stage IV CRC.

BACKGROUND:Serum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC. METHODS:Patients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis. RESULTS:We included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040). CONCLUSIONS:Early postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

［Abstract］ For the past few years, a complete theory and twenty different procedures have been developed for natural orifice specimen extraction surgery (NOSES). However, ensuring aseptic and tumor-free procedure in NOSES remains to be a controversial topic. Based on the clinical practice experience of the author’s centre, combined with domestic and foreign literature reports, this paper reviews the issues related to the standardized aseptic and tumor-free procedure in NOSES, in order to provide reference for the clinical practice of NOSES.

Cancer stemness, chemoresistance, and metastasis are related biological events. However, whether they have common molecular mechanisms remains to be determined. Here, we report that imiquimod (IMQ) facilitates the acquisition of stem-cell-like properties and chemoresistance via the upregulation of matrix metalloproteinase 1 (MMP1) and downregulation of microRNA-145 (miR-145). MiR-145-5p was found to suppress MMP1 expression through direct binding, and miR-145-mediated downregulation of MMP1 reversed the effects of IMQ. In addition, IMQ downregulated miR-145 by promoting DNA methylation at its promoter. DNA methyltransferase inhibitors limited IMQ-induced MMP1 expression, stemness, and chemoresistance. Collectively, our results highlight the miR-145-MMP1 axis as a potential coordinator of cancer stemness and chemoresistance. Given the role of MMP1 in the initiation of metastasis, the miR-145-MMP1 axis serves as a promising therapeutic target for improved cancer treatment.

Due to advances in understanding the immune microenvironment of colorectal cancer (CRC), microsatellite classification (dMMR/MSI-H and pMMR/MSS) has become a key biomarker for the diagnosis and treatment of CRC patients and therefore has important clinical value. Microsatellite status is associated with a variety of clinicopathological features and affects drug resistance and the prognosis of patients. CRC patients with different microsatellite statuses have different compositions and distributions of immune cells and cytokines within their tumor microenvironments (TMEs). Therefore, there is great interest in reversing or reshaping CRC TMEs to transform immune tolerant "cold" tumors into immune sensitive "hot" tumors. This requires a thorough understanding of differences in the immune microenvironments of MSI-H and MSS type tumors. This review focuses on the relationship between CRC microsatellite status and the immune microenvironment. It focuses on how this relationship has value for clinical application in diagnosis and treatment, as well as exploring the limitations of its current application.

Cancer-derived exosomal miRNAs play an important role in the development of metastasis, but the effects and underlying mechanisms remain unclear. In the present study, we investigated the miRNA expression profiles of 5 paired serum exosomal samples from metastatic colorectal cancer (mCRC) and non-mCRC patients via RNA sequencing. After we evaluated the differentially expressed miRNAs in 80 CRC patients, miR-106b-3p was selected as a metastasis-associated miRNA of CRC. We showed that the expression level of serum exosomal miR-106b-3p was significantly higher in CRC patients with metastasis than those without metastasis. Additionally, high serum exosomal miR-106b-3p expression in patients was correlated with a poor prognosis. Coculture of low-metastatic CRC cells with high-metastatic CRC cell-derived exosomes promoted cell migration, invasion, and epithelial-to-mesenchymal transition (EMT), which was caused by the transport and transduction of miR-106b-3p in vitro. Moreover, exosomal miR-106b-3p promoted lung metastasis of CRC cells in vivo. In addition, we demonstrated that miR-106b-3p regulated metastasis by targeting deleted in liver cancer-1 (DLC-1). A negative correlation was also identified between miR-106b-3p and DLC-1 expression in human CRC tumour tissues and in mouse lung metastatic lesions. Collectively, our study indicated that metastasis-associated miR-106b-3p from serum exosomes could be used as a potential prognostic biomarker and therapeutic target for CRC patients.