STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer

Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Colorectal cancer screening:A review of current knowledge and progress in research

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Recent clinical trials and optical control as a potential strategy to develop microtubule-targeting drugs in colorectal cancer management

Colorectal cancer(CRC)has remained the second and the third leading cause of cancer-related death worldwide and in the United States,respectively.Although significant improvement in overall survival has been achieved,death in adult populations under the age of 55 appears to have increased in the past decades.Although new classes of therapeutic strategies such as immunotherapy have emerged,their application is very limited in CRC so far.Microtubule(MT)inhibitors such as taxanes,are not generally successful in CRC.There may be some way to make MT inhibitors work effectively in CRC.One potential advantage that we can take to treat CRC may be the combination of optical techniques coupled to an endoscope or other fiber optics-based devices.A combination of optical devices and photo-activatable drugs may allow us to locally target advanced CRC cells with highly potent MT-targeting drugs.In this Editorial review,we would like to discuss the potential of optogenetic approaches in CRC management.

Non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of colorectal cancer

The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of those affected are diagnosed later,in advanced stages.The efficacy of screening programs has been well-established for several years,which reduces the risk of CRC morbidity and mortality,without taking into account the test used for screening,or other tools.Nevertheless,a significant proportion of patients remain unscreened,so understanding the factors involved,as well as the barriers of the population to adherence is the first step to possibly modify the participation rate.These barriers could include a full range of social and political aspects,especially the type of financial provision of each health service.In Japan,health services are universal,and this advantageous situation makes it easier for citizens to access to these services,contributing to the detection of various diseases,including CRC.Interestingly,the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities,and symptomatic and cancer screening groups showed similar early-stage diagnosis.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer

Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein synthesis.SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human diseases.It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in patients.On the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer type.Recent research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous conditions.Consequently,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC.Nevertheless,current comprehension of the potential roles of snoRNAs in CRC remains limited.This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Colorectal cancer screening: Modalities and adherence

In the last decade,several studies have explored various modalities and strategies for colorectal cancer(CRC)screening,taking into account epidemiological data,individual characteristics,and socioeconomic factors.In this editorial,we comment further on a retrospective study by Agatsuma et al published in the recent issue of the World Journal of Gastroenterology.Our focus is on screening trends,particularly in relation to efforts to improve the currently suboptimal uptake among the general population worldwide,aiming to enhance early diagnosis rates of CRC.There is a need to raise awareness through health edu-cation programs and to consider the use of readily available,non-invasive screening methods.These strategies are crucial for attracting screen-eligible populations to participate in first-line screening,especially those in high-or average-risk groups and in regions with limited resources.Liquid biopsies and biomarkers represent rapidly evolving trends in screening and diagnosis;however,their clinical relevance has yet to be standardized.

Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older people.Surgical management,despite advancements,requires careful consideration of preoperative patient status for optimal outcomes.AIM To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery.METHODS A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis.Only studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were included.Pooled effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were included.Compared with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow up.Frail patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control group.The risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail patients.CONCLUSION Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased mortality.Integrating frailty assessment appears crucial for tailored surgical management.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer

BACKGROUND Identifying patients with peritoneal metastasis(PMs)of colorectal cancer(CRC)who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery.Inflammatory and nutritional indicators play essential roles in cancer development and metastasis.AIM To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM.METHODS We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018.Patients’demographics,overall survival(OS),and preoperative inflammatory and nutritional markers were evaluated.The Kaplan-Meier method and log-rank test were used to estimate differences.RESULTS Of the 133 patients,94(70.6%)had normal hemoglobin(Hb)and 54(40.6%)had a high neutrophil-to-lymphocyte ratio(NLR).The median OS(mOS)was significantly lower for patients with high NLR(7.9 months)than for those with low NLR(25.4 months;P=0.002).Similarly,patients with normal Hb had a longer mOS(18.5 months)than those with low Hb(6.3 months;P<0.001).Multivariate analysis identified age,carbohydrate antigen 199 levels,NLR,Hb,and peritoneal cancer index as independent predictors of OS.Based on these findings,a nomogram was constructed,which demonstrated a good capacity for prediction,with a C-index of 0.715(95%confidence interval:0.684-0.740).Furthermore,the 1-and 2-year survival calibration plots showed good agreement between predicted and actual OS rates.The areas under the curve for the 1-and 2-year survival predictions of the nomogram were 0.6238 and 0.6234,respectively.CONCLUSION High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM.The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM,indicating its potential as a valuable prognostic tool for this patient population.

OSW-1 triggers necroptosis in colorectal cancer cells through the RIPK1/RIPK3/MLKL signaling pathway facilitated by the RIPK1- p62/SQSTM1 complex

BACKGROUND Necroptosis has emerged as a novel molecular pathway that can be targeted by chemotherapy agents in the treatment of cancer.OSW-1,which is derived from the bulbs of Ornithogalum saundersiae Baker,exerts a wide range of pharmaco-logical effects.AIM To explore whether OSW-1 can induce necroptosis in colorectal cancer(CRC)cells,thereby expanding its range of clinical applications.METHODS We performed a sequence of functional experiments,including Cell Counting Kit-8 assays and flow cytometry analysis,to assess the inhibitory effect of OSW-1 on CRC cells.We utilized quantitative proteomics,employing tandem mass tag label-ing combined with liquid chromatography-tandem mass spectrometry,to analyze changes in protein expression.Subsequent bioinformatic analysis was conducted to elucidate the biological processes associated with the identified proteins.Transmission electron microscopy(TEM)and immunofluorescence studies were also performed to examine the effects of OSW-1 on necroptosis.Finally,western blotting,siRNA experiments,and immunoprecipitation were employed to evaluate protein interactions within CRC cells.RESULTS The results revealed that OSW-1 exerted a strong inhibitory effect on CRC cells,and this effect was accompanied by a necroptosis-like morphology that was observable via TEM.OSW-1 was shown to trigger necroptosis via activation of the RIPK1/RIPK3/MLKL pathway.Furthermore,the accumulation of p62/SQSTM1 was shown to mediate OSW-1-induced necroptosis through its interaction with RIPK1.CONCLUSION We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway,and that this effect is mediated by the RIPK1-p62/SQSTM1 complex,in CRC cells.These results provide a theoretical foundation for the use of OSW-1 in the clinical treatment of CRC.

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

BACKGROUND Pyroptosis impacts the development of malignant tumors,yet its role in colorectal cancer(CRC)prognosis remains uncertain.AIM To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration.METHODS Gene expression data were obtained from The Cancer Genome Atlas(TCGA)and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus(GEO).Pyroptosis-related gene expression in cell clusters was analyzed,and enrichment analysis was conducted.A pyroptosis-related risk model was developed using the LASSO regression algorithm,with prediction accuracy assessed through K-M and receiver operating characteristic analyses.A nomo-gram predicting survival was created,and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations.Finally,the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database.RESULTS An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B,SDHB,BST2,UBE2D2,GJA1,AIM2,PDCD6IP,and SEZ6L2(P<0.05).Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis(P<0.05).Patients with higher risk scores demonstrated increased death risk and reduced overall survival(P<0.05).Significant differences in immune infiltration were observed between low-and high-risk groups,correlating with pyroptosis-related gene expression.CONCLUSION We developed a pyroptosis-related prognostic model for CRC,affirming its correlation with immune infiltration.This model may prove useful for CRC prognostic evaluation.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

Global research trends and prospects of cellular metabolism in colorectal cancer

BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

Leukocyte immunoglobulin-like receptor B2:A promising biomarker for colorectal cancer

According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.