Colorectal Tumors Research Articles

Enhanced theranostic efficacy of epirubicin-loaded SPION@MSN through co-delivery of an anti-miR-21-expressing plasmid and ZIF-8 hybridization to target colon adenocarcinoma.

Using targeted drug delivery systems has emerged as a promising approach to increase the efficacy of chemotherapy, particularly in combination with gene therapy. The overexpression of miR-21 plays a crucial role in colorectal cancer (CRC) progression, and targeted inhibition of miR-21 offers significant potential for enhancing CRC chemotherapy outcomes. In this study, a theranostic system based on mesoporous silica and superparamagnetic iron oxide nanoparticles (SPION@MSNs) was synthesized as a core-shell structure. After loading epirubicin (EPI) in the open pores of MSN, the plasmid expressing anti-miR-21 (pDNA) covered the outer surface with the help of a ZIF-8 (zeolitic imidazolate framework-8) film. Afterward, polyethylene glycol (PEG) and AS1411 aptamer were conjugated to the surface to improve the protective, biocompatibility, and targeting abilities of the nanocarrier. Moreover, the physicochemical characteristics as well as the loading capacity and release profile of EPI and pDNA were fully evaluated. The uptake of the nanoparticles by CRC and normal cell lines in addition to the anticancer effects related to targeted combinational therapy were investigated in vitro. Finally, in vivo tests were performed on BALB/c mice bearing colorectal tumors to evaluate the effectiveness of the targeted nanoparticles, their possible side effects, and also their application in fluorescence and magnetic imaging in vivo. The successful synthesis of SPION@MSN-EPI/pDNA-ZIF-8-PEG-Apt nanoparticles (∼68 nm) and good loading efficiency and controlled release of EPI and pDNA were confirmed. Moreover, hemolysis and gel retardation assays demonstrated the biocompatibility and plasmid protection. Cellular uptake and expression of copGFP illustrated selective entry and transient transfection of targeted nanoparticles, consistent with the cytotoxicity results that indicated the synergistic effects of chemo-gene therapy. The results of animal studies proved the high antitumor efficiency of targeted nanoparticles with minimal tissue damage, which was in line with fluorescence and magnetic imaging results. The novel synthesized nanoparticles containing SPION@MSN-ZIF-8 were suitable for CRC theranostics, and the combined approach of chemo-gene therapy suppressed the tumor more effectively.

Assessing the effectiveness of targeted agents in adjuvant therapy for patients with metastatic colorectal cancer undergoing surgical resection: a retrospective cohort study.

Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Retrospective cohort study. Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

HDAC6 inhibitor ACY-1215 enhances STAT1 acetylation to block PD-L1 for colorectal cancer immunotherapy

The search for effective combination therapy with immune checkpoint inhibitors (ICI) has become important for cancer patients who do not respond to the ICI well. Histone deacetylases (HDACs) inhibitors have attracted wide attention as anti-tumor agents. ACY-1215 is a selective inhibitor of HDAC6, which can inhibit the growth of a variety of tumor. We previously revealed that HDAC family is highly expressed in colorectal cancer specimens and mouse models. In this study, ACY-1215 was combined with anti-PD1 to treat tumor-bearing mice associated with colorectal cancer. ACY-1215 combined with anti-PD1 effectively inhibited the colorectal tumor growth. The expression of PD-L1 in tumor of mice were inhibited by ACY-1215 and anti-PD1 combination treatment, whereas some biomarkers reflecting T cell activation were upregulated. In a co-culture system of T cells and tumor cells, ACY-1215 helped T cells to kill tumor cells. Mechanically, HDAC6 enhanced the acetylation of STAT1 and inhibited the phosphorylation of STAT1, thus preventing STAT1 from entering the nucleus to activate PD-L1 transcription. This study reveals a novel regulatory mechanism of HDAC6 on non-histone substrates, especially on protein acetylation. HDAC6 inhibitors may be of great significance in tumor immunotherapy and related combination strategies.

Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Analysis of effect of colonoscopy combined with laparoscopy in the treatment of colorectal tumors.

Colorectal cancer is one of the most common digestive tract tumors. To evaluate the feasibility and safety of laparoscopic colorectal cancer surgery. This study retrospectively analyzed early postoperative clinical data of 48 patients with colorectal cancer treated in our hospital between 2015 and 2021, of which 21 underwent laparoscopic colorectal surgery, and 27 underwent laparotomy. There was no significant difference in clinical data. Patients were included if they had colorectal cancer (confirmed by colonoscopy and biopsy pathological examination before surgery), were evaluated for possible radical surgery before surgery, and had no intestinal obstruction, tumor invasion of adjacent organs (by digital rectal examination and preoperative abdominal color Doppler ultrasound, CT confirmed) and no other history of abdominal surgery. Using the method of clinical control study, operation time, intraoperative blood loss, postoperative general condition, surgical lymph node removal (postoperative pathology), surgical complications, gastrointestinal function recovery, surgical before and after blood glucose, body temperature, white blood cells, pain visual analog scale (VAS) and other conditions were compared and analyzed to determine feasibility and safety of laparoscopic surgery for colorectal cancer. Colorectal cancer was successfully removed by laparoscopic radical resection without any significant problems or surgical fatalities. Age, gender, tumor location, stage, and duration of surgery did not differ between laparoscopic and laparotomy operations. Compared to laparotomy, postoperative eating, bowel movements, and blood sugar levels improved. Variations in the length of surgically removed specimens after VAS measurements revealed open and laparoscopic operations. The overall lymph node count was 10.8 ± 1.6, with no variation between the two techniques. Laparoscopic colorectal cancer radical surgery is safe and feasible. Also, it has the advantages of minimally invasive surgery. Laparoscopic colorectal cancer radical surgery can comply with the principles of oncology revolutionary.

The expression of UNC5D is abnormal in the early stage of colorectal tumors associated with its proliferation and migration.

Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression.

Immunohistochemistry staining for DNA mismatch repair proteins in endoscopic biopsies and the corresponding surgical specimen in colorectal cancer.

Microsatellite instability is found in 15% of sporadic colorectal cancers (CRC) and 95% of hereditary CRC cases. Lynch syndrome (LS) diagnosis begins with the analysis of the surgical specimen using methods such as immunohistochemistry (IHC), which identifies changes in the nuclear expression of DNA mismatch repair (MMR) proteins. However, IHC analysis on endoscopic biopsies could provide substantial benefits. Our goal was to assess the accuracy of MMR IHC status on endoscopic biopsies in comparison to corresponding surgical specimen in a series of CRC. We retrospectively selected patients who had undergone CRC surgery between February 2011 and January 2020 and had IHC testing for MMR proteins on the surgical specimen. The study was then performed on the corresponding endoscopic biopsies and results were compared. MMR IHC staining on surgical specimens were available for 361 CRC patients and only in 154 cases for preoperative endoscopic biopsies. The concordance between MMR IHC status of the endoscopic biopsy and the surgical specimen analysis was 98.6% for the MLH1/PMS2 proteins and 100% for MSH2/MSH6. In conclusion, endoscopic biopsies of colorectal tumors serve as a suitable tissue source for the immunohistochemical analysis of DNA repair proteins. The correlation with results from the surgical specimen was notably high and discrepancies were primarily as a result of intratumoral heterogeneity within the same sample. The features of MMR protein loss in endoscopic biopsies can provide clinicians with valuable information for specific therapeutic approaches and genetic counseling.

A Case of Colorectal Tumor Complicated with Left Iliac Vein Compression Syndrome

A Case of Colorectal Tumor Complicated with Left Iliac Vein Compression Syndrome

Efficacy and safety of probiotics, prebiotics, and synbiotics for the prevention of colorectal cancer and precancerous lesion in high-risk populations: A systematic review and meta-analysis of randomized controlled trials.

Colorectal cancer (CRC) is highly prevalent worldwide and is a leading cause of cancer-related death. Probiotics, prebiotics, and synbiotics have recently attracted attention as preventive measures against colorectal neoplasms. We aimed to analyze the findings of randomized controlled trials (RCTs) on the effects of probiotics, prebiotics, and synbiotics in patients at a high risk of CRC, outlining the challenges and future prospects of using probiotics to prevent colorectal tumors and providing evidence for clinical physicians in particular. PubMed, EMBASE, and the Cochrane Library databases were searched for relevant studies published up to January 7, 2022. RCTs conducted on populations with a high risk of CRC who received probiotics, prebiotics or synbiotics in comparisonwith placebo, candidate agent or no treatment were included. The primary outcome was the incidence or recurrence of any colorectal neoplasms. Additional outcomes included their effects on the diversity of gut microbiota and relevant inflammatory biomarkers. Safety outcomes were also analyzed. Two authors independently screened and selected studies based on pre-specified eligible criteria, performed data extraction and risk-of-bias assessment independently. Nine RCTs were included in the systematic review and meta-analysis. Probiotic supplementation significantly reduced adenoma incidence, but no significant benefit was observed in CRC incidence. Additionally, probiotics modulated gut microbiota and inflammatory biomarkers. Probiotics may have beneficial effects in the prevention of CRC. More RCTs with larger sample sizes are warranted to further confirm these findings.

LncRNA CRNDE Drives the Progression of Hepatocellular Carcinoma by inducing the Immunosuppressive Niche.

As a crucial protumorigenic long noncoding RNA, colorectal tumor differential expression (CRNDE) has been confirmed to facilitate the progression of various cancers. However, its role in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) is still unclear. Here we determined that CRNDE was upregulated in HCC samples and that CRNDE-positive cells were predominantly enriched in malignant tumor cells. In vivo functional assays revealed that CRNDE-induced tumor cells supported HCC progression, recruited abundant granulocyte myeloid-derived suppressor cells (G-MDSCs) and restricted the infiltration of T cells. In terms of mechanisms, CRNDE bound with Toll-like receptor 3 (TLR3) and activated NF-κB signaling to increase the secretion of c-x-c motif chemokine ligand 3 (CXCL3). CRNDE knockdown could significantly suppress the accumulation of G-MDSCs and enhance the infiltration of T cells in the TME of HCC in vivo. Taken together, our study reveals the CRNDE-NF-κB-CXCL3 axis plays a crucial role in driving the immunosuppressive niche to facilitate HCC progression by recruiting G-MDSCs.

Dickkopf 1 is expressed in normal fibroblasts during early stages of colorectal tumorigenesis.

Colorectal cancer progression from adenoma to cancer is a time-intensive process; however, the interaction between normal fibroblasts (NFs) with early colorectal tumors, such as adenomas, remains unclear. Here, we analyzed the response of the microenvironment during early tumorigenesis using co-cultures of organoids and NFs. Colon normal epithelium, adenoma, cancer organoid, and NFs were established and co-cultured using Transwell inserts. Microarray analysis of NFs was performed to identify factors expressed early in tumor growth. Immunostaining of clinical specimens was performed to localize the identified factor. Functional analysis was performed using HCT116 cells. Serum DKK1 levels were measured in patients with colorectal cancer and adenoma. Colorectal organoid-NF co-culture resulted in increased organoid diameter and cell viability in normal epithelial and adenomatous organoids but not in cancer organoids. Microarray analysis of NFs revealed 18 genes with increased expression when co-cultured with adenoma and cancer organoids. Immunohistochemical staining revealed DKK1 expression in the tumor stroma from early tumor growth. DKK1 stimulation reduced HCT116 cell proliferation, while DKK1 silencing by siRNA transfection increased cell proliferation. Serum DKK1 level was significantly higher in patients with advanced cancer and adenoma than in controls. Serum DKK1 level revealed area-under-the-curve values of 0.78 and 0.64 for cancer and adenoma, respectively. These findings contribute valuable insights into the early stages of colorectal tumorigenesis and suggest DKK1 as a tumor suppressor. Additionally, serum DKK1 levels could serve as a biomarker to identify both cancer and adenoma, offering diagnostic possibilities for early-stage colon tumors. The present study has a few limitations. We considered using DKK1 as a candidate gene for gene transfer to organoids and NFs; however, it was difficult due to technical problems and the slow growth rate of NFs. Therefore, we used cancer cell lines instead. In addition, immunostaining and ELISA were based on the short-term collection at a single institution, and further accumulation of such data is desirable. As described above, most previous reports were related to advanced cancers, but in this study, new findings were obtained by conducting experiments on endoscopically curable early-stage tumors, such as adenomas.

Treatment options for HER2-expressing colorectal cancer: updates and recent approvals.

Colorectal cancer is a leading cause of cancer-related mortality worldwide. Approximately 3-5% of colorectal tumors harbor human epidermal growth factor receptor (HER2) amplification which is associated with a higher incidence of intracranial metastasis and overall worse outcomes. In the setting of refractory metastatic RAS wild-type tumors, evidence supports the use of various HER2-blocking agents, including monoclonal antibodies, tyrosine kinase inhibitors, and novel antibody-drug conjugates. With a number of relatively active agents clinically available and even more in development, it is crucial for clinicians to familiarize themselves with the mechanisms of action, efficacy data, and safety profiles of these treatments. In this review, we aim to summarize key findings from past and ongoing trials with anti-HER2 agents in metastatic colorectal cancer.

Interleukin-17 directly stimulates tumor infiltrating Tregs to prevent cancer development.

Interleukin-17 (IL-17) family cytokines promote protective inflammation for pathogen resistance, but also facilitate autoimmunity and tumor development. A direct signal of IL-17 to regulatory T cells (Tregs) has not been reported and may help explain these dichotomous responses. We generated a conditional knockout of Il17ra in Tregs by crossing Foxp3-YFP-Cre mice to Il17ra-flox mice (Il17ra ΔTreg mice). Subsequently, we adoptively transferred bone marrow cells from Il17ra ΔTreg mice to a mouse model of sporadic colorectal cancer (Cdx2-Cre +/Apc F/+), to selectively ablate IL-17 direct signaling on Tregs in colorectal cancer. Single cell RNA sequencing and bulk RNA sequencing were performed on purified Tregs from mouse colorectal tumors, and compared to those of human tumor infiltrating Treg cells. IL-17 Receptor A (IL-17RA) is expressed in Tregs that reside in mouse mesenteric lymph nodes and colon tumors. Ablation of IL-17RA, specifically in Tregs, resulted in increased Th17 cells, and exacerbated tumor development. Mechanistically, tumor-infiltrating Tregs exhibit a unique gene signature that is linked to their activation, maturation, and suppression function, and this signature is in part supported by the direct signaling of IL-17 to Tregs. To study pathways of Treg programming, we found that loss of IL-17RA in tumor Tregs resulted in reduced RNA splicing, and downregulation of several RNA binding proteins that are known to regulate alternative splicing and promote Treg function. IL-17 directly signals to Tregs and promotes their maturation and function. This signaling pathway constitutes a negative feedback loop that controls cancer-promoting inflammation in CRC.

Role of HER2/neu in Colorectal Carcinoma: A Cross-sectional Study from a Tertiary Care Centre in West Bengal, India

Introduction: In many tumours, Human Epidermal Growth Factor Receptor 2 (HER2) expression and HER2 amplification are studied as therapeutic and prognostic factors. The incidence of HER2/neu expression and its consequences in patients with colorectal carcinoma has shown conflicting evidence. Aim: To evaluate the utility of HER2/neu expression in colorectal carcinoma and to find any association between HER2/neu expression, histological grade, and stage of the tumour. Materials and Methods: This cross-sectional study was conducted on 50 cases of colorectal carcinoma. Patients undergoing surgery for colorectal tumours were selected over an 18-month period (January 2020 to June 2021) in a tertiary care hospital in Kolkata, West Bengal, India. Various clinical and demographic parameters were obtained from the patients, and the specimens were subjected to Immunohistochemical (IHC) staining for HER2/neu. The results were analysed using Statistical Package for the Social Sciences (SPSS)software version 25.0 (IBM, Armonk, New York, USA). Results: On HER2/neu IHC examination, 30 cases (60%) showed a 3+ score, 4 cases (8%) showed a 2+ score, 7 cases (14%) showed a 1+ score, and the remaining 9 cases (18%) showed a score of 0. HER2/neu expression was found in 30 cases (60%) of colorectal carcinoma. HER2/neu expression showed a significant association with the histological grade of the tumour (p-value=0.020). HER2/neu expression also showed a significant association (p-value<0.001) with histological subtypes of the tumour. Conclusion: This study revealed a significant association between HER2/neu expression and histological subtypes and grade of the tumour. Moderately differentiated adenocarcinoma showed the highest expression, while mucinous adenocarcinoma and undifferentiated carcinoma showed minimal or absent HER2/ neu expression. Thus, HER2/neu can serve as a prognostic and therapeutic marker in colorectal carcinoma. In conclusion, surgery alone is not curative for patients with colorectal cancer, and additional forms of management may be required to improve patient survival. In such cases, HER2/neu expression can guide new adjuvant therapy.

Characterization of Natural Killer cells infiltrating irradiated murine tumors through flow cytometry.

The radiation-induced immune response is increasingly well documented. However, some aspects remain unclear, notably the role of Natural Killer (NK) cells, a subgroup of innate lymphoid cells involved in the antitumor response, in the response to RT. It therefore seems necessary to better characterize NK cells infiltrating irradiated tumors in order to better understand the mechanisms of action of RT, enabling its subsequent optimization and combination with other immunomodulatory treatments. A key technology for studying intratumoral immune cells is flow cytometry, which can simultaneously quantify and analyze the phenotype of numerous cells. Here, we propose a method for phenotyping intratumoral NK cells through flow cytometry in mice bearing colorectal tumors treated with radiotherapy. This procedure can also be used to study the radiation-induced NK cell response in a wide range of solid tumors.

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-β-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis.

Anoikis is a speed-limited procedure to inhibit tumor metastasis during epithelial-mesenchymal transition (EMT). Previous studies have explored anoikis-related genes (ARG) in predicting prognosis and distinguishing tumoral immunity in many types of cancer. However, the role of ARGs in regulating NK cell exhaustion (NKE) and in predicting chemotherapy sensitivity is not clear. Therefore, it is necessary to work on it. Gene expression profiles and clinical features are collected from TCGA and GEO, and data analysis is performed in R4.2.0. The ARGs-based no-supervised learning algorithm identifies three ARG subgroups, amongst which the prognosis is different. WCGNA and Artificial intelligence (AI) are applied to construct an NKE-related drug sensitivity stratification and prognosis identification model in digestive system cancer. Pathways association analysis screens out GLI2 is a key gene in regulating NKE by non-classic Hedgehog signaling (GLI2/TGF-β/IL6). In vitro experiments show that down-regulation of GLI2 enhances the CAPE-mediated cell toxicity and accompanies with down-regulation of PD-L1, tumor-derive IL6, and snial1 whereas the expression of cleaved caspas3, cleaved caspase4, cleaved PARP, and E-cadherin are up-regulated in colorectal cancer. Co-culture experiments show that GLI2- decreased colorectal tumor cells lead to down-regulation of TIM-3 and PD1 in NK cells, which are restored by TGF-bate active protein powder. Besides, the Elisa assay shows that GLI2-decreased colorectal tumor cells lead to up-regulation of IFN-gamma in NK cells.

Muscle-related parameters-based machine learning model for predicting postinduction hypotension in patients undergoing colorectal tumor resection surgery.

This study used machine learning algorithms to identify important variables and predict postinduction hypotension (PIH) in patients undergoing colorectal tumor resection surgery. Data from 318 patients who underwent colorectal tumor resection under general anesthesia were analyzed. The training and test sets are divided based on the timeline. The Boruta algorithm was used to screen relevant basic characteristic variables and establish a model for the training set. Four models, regression tree, K-nearest neighbor, neural network, and random forest (RF), were built using repeated cross-validation and hyperparameter optimization. The best model was selected, and a sorting chart of the feature variables, a univariate partial dependency profile, and a breakdown profile were drawn. R2, mean absolute error (MAE), mean squared error (MSE), and root MSE (RMSE) were used to plot regression fitting curves for the training and test sets. The basic feature variables associated with the Boruta screening were age, sex, body mass index, L3 skeletal muscle index, and HUAC. In the optimal RF model, R2 was 0.7708 and 0.7591, MAE was 0.0483 and 0.0408, MSE was 0.0038 and 0.0028, and RMSE was 0.0623 and 0.0534 for the training and test sets, respectively. A high-performance algorithm was established and validated to demonstrate the degree of change in blood pressure after induction to control important characteristic variables and reduce PIH occurrence.

Expert consensus on the early diagnosis and treatment of colorectal cancer in China (2023 edition)

Colorectal cancer (CRC) has been a common malignant tumor in China. Through the great effort in cancer prevention and treatment, the 5-year survival rate of patients with CRC in China has been largely improved. However, insufficient early diagnosis and treatment have seriously impeded the prognosis of Chinese CRC patients. The Early Diagnosis and Treatment Group of the Chinese Medical Association, Oncology Branch organized experts in the area of CRC to write the Expert Consensus on the Early Diagnosis and Treatment of Colorectal Cancer in China and issued it publicly (2020 edition). The 2020 edition of expert consensus has been meaningful to the early diagnosis and standardized treatment of CRC. Based on the prior edition, the Early Diagnosis and Treatment Group of the Chinese Medical Association, Oncology Branch revise the consensus focused on the early screening and diagnosis protocols for colorectal cancer, endoscopic/surgical management of early colorectal tumor, as well as adjuvant treatment and remedial measures and follow-up monitoring protocols. The 2023 edition of the consensus not only synthesized the latest evidence from China and combined it with the specific national condition and clinical practice, but also referred to the international guidelines. This 2023 edition consensus, developed for clinicians working on the screening, early diagnosis and treatment for CRC, would further promote the standardization and advances in the diagnosis and treatment of CRC at the early stage in China, and improve the survival and prognosis of CRC.

Pirin Inhibits FAS-Mediated Apoptosis to Support Colorectal Cancer Survival.

Resistance to immunotherapy in colorectal cancer (CRC) is associated with obstruction of FAS (Apo-1 or CD95)-dependent apoptosis, a hallmark of cancer. Here it is demonstrated that the upregulation of pirin (PIR) protein in colon cancers promotes tumorigenesis. Knockout or inhibition of PIR dramatically increases FAS expression, FAS-dependent apoptosis and attenuates colorectal tumor formation in mice. Specifically, NFκB2 is a direct transcriptional activator of FAS and robustly suppressed by PIR in dual mechanisms. One is the disruption of NFκB2 complex (p52-RELB) association with FAS promoter, the other is the inhibition of NIK-mediated NFκB2 activation and nuclear translocation, leading to the inability of active NFκB2 complex toward the transcription of FAS. Furthermore, PIR interacts with FAS and recruits it in cytosol, preventing its membrane translocation and assembling. Importantly, knockdown or knockout of PIR dramatically sensitizes cells to FAS mAb- or active CD8+ T cells-triggered cell death. Taken together, a PIR-NIK-NFκB2-FAS survival pathway is established, which plays a key role in supporting CRC survival.

Determination of dimethylated nucleosides in serum from colorectal cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry

RNA modifications play a crucial regulatory role in a variety of biological processes and are closely related to numerous diseases, including cancer. The diversity of metabolites in serum makes it a favored biofluid for biomarkers discovery. In this work, a robust and accurate hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach was established for simultaneous determination of dimethylated nucleosides in human serum. Using the established method, we were able to accurately quantify the concentrations of N6-2′-O-dimethyladenosine (m6Am), N2,N2-dimethylguanosine (m2,2G), and 5,2′-O-dimethyluridine (m5Um) in serum samples from 53 healthy controls, 57 advanced colorectal adenoma patients, and 39 colorectal cancer (CRC) patients. The results showed that, compared with healthy controls and advanced colorectal adenoma patients, the concentrations of m6Am and m2,2G were increased in CRC patients, while the concentration of m5Um was decreased in CRC patients. These results indicate that these three dimethylated nucleosides could be potential biomarkers for early detection of colorectal cancer. Interestingly, the level of m5Um was gradually decreased from healthy controls to advanced colorectal adenoma patients to CRC patients, indicating m5Um could also be used to evaluate the level of malignancy of colorectal tumor. In addition, this study will contribute to the investigation on the regulatory mechanisms of RNA dimethylation in the onset and development of colorectal cancer.