The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expr...Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.展开更多
Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastr...Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.展开更多
Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metasta...Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.展开更多
BACKGROUND Metastatic colorectal cancer(mCRC)is a common malignancy whose treatment has been a clinical challenge.Cancer-specific survival(CSS)plays a crucial role in assessing patient prognosis and treatment outcomes...BACKGROUND Metastatic colorectal cancer(mCRC)is a common malignancy whose treatment has been a clinical challenge.Cancer-specific survival(CSS)plays a crucial role in assessing patient prognosis and treatment outcomes.However,there is still li-mited research on the factors affecting CSS in mCRC patients and their corre-lation.AIM To predict CSS,we developed a new nomogram model and risk grading system to classify risk levels in patients with mCRC.METHODS Data were extracted from the United States Surveillance,Epidemiology,and End Results database from 2018 to 2023.All eligible patients were randomly divided into a training cohort and a validation cohort.The Cox proportional hazards model was used to investigate the independent risk factors for CSS.A new nomogram model was developed to predict CSS and was evaluated through internal and external validation.RESULTS A multivariate Cox proportional risk model was used to identify independent risk factors for CSS.Then,new CSS columns were developed based on these factors.The consistency index(C-index)of the histogram was 0.718(95%CI:0.712-0.725),and that of the validation cohort was 0.722(95%CI:0.711-0.732),indicating good discrimination ability and better performance than tumor-node-metastasis staging(C-index:0.712-0.732).For the training set,0.533,95%CI:0.525-0.540;for the verification set,0.524,95%CI:0.513-0.535.The calibration map and clinical decision curve showed good agreement and good potential clinical validity.The risk grading system divided all patients into three groups,and the Kaplan-Meier curve showed good stratification and differentiation of CSS between different groups.The median CSS times in the low-risk,medium-risk,and high-risk groups were 36 months(95%CI:34.987-37.013),18 months(95%CI:17.273-18.727),and 5 months(95%CI:4.503-5.497),respectively.CONCLUSION Our study developed a new nomogram model to predict CSS in patients with synchronous mCRC.In addition,the risk-grading system helps to accurately assess patient prognosis and guide treatment.展开更多
BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as...BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as albumin bilirubin(ALBI)score,liver function index,and carcinoembryonic antigen(CEA)have shown some potential in the prediction of liver metastasis but have not been fully explored.AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI,liver function index,and CEA,and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months.According to the follow-up results,the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1.The risk factors for liver metastasis in patients with CRC were analyzed,a prediction model was constructed by least absolute shrinkage and selection operator(LASSO)logistic regression,internal validation was performed by the bootstrap method,the reliability of the prediction model was evaluated by subject-work characteristic curves,calibration curves,and clinical decision curves,and a column graph was drawn to show the prediction results.RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria.Through LASSO regression variable screening and logistic regression analysis.The ALBI score,alanine aminotransferase(ALT),and CEA were found to be independent predictors of liver metastases in CRC patients[odds ratio(OR)=8.062,95%confidence interval(CI):2.545-25.540],(OR=1.037,95%CI:1.004-1.071)and(OR=1.025,95%CI:1.008-1.043).The area under the receiver operating characteristic curve(AUC)for the combined prediction of CRLM in the modeling group was 0.921,with a sensitivity of 78.0%and a specificity of 95.0%.The H-index was 0.921,and the H-L fit curve hadχ^(2)=0.851,a P value of 0.654,and a slope of the calibration curve approaching 1.This indicates that the model is extremely accurate,and the clinical decision curve demonstrates that it can be applied effectively in the real world.We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method.The AUC was 0.913,while the accuracy was 0.869 and the kappa consistency was 0.709.The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918,sensitivity of 85.0%,specificity of 95.6%,C-index of 0.918,and an H-L fitting curve withχ^(2)=0.586,P=0.746.CONCLUSION The ALBI score,ALT level,and CEA level have a certain value in predicting liver metastasis in patients with CRC.These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC.The risk prediction model developed in this work shows great potential for practical application.展开更多
BACKGROUND Synchronous liver metastasis(SLM)is a significant contributor to morbidity in colorectal cancer(CRC).There are no effective predictive device integration algorithms to predict adverse SLM events during the ...BACKGROUND Synchronous liver metastasis(SLM)is a significant contributor to morbidity in colorectal cancer(CRC).There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC.AIM To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix(GLCM)features collected from magnetic resonance imaging(MRI).METHODS Our study retrospectively enrolled 392 patients with CRC from Yichang Central People’s Hospital from January 2015 to May 2023.Patients were randomly divided into a training and validation group(3:7).The clinical parameters and GLCM features extracted from MRI were included as candidate variables.The prediction model was constructed using a generalized linear regression model,random forest model(RFM),and artificial neural network model.Receiver operating characteristic curves and decision curves were used to evaluate the prediction model.RESULTS Among the 392 patients,48 had SLM(12.24%).We obtained fourteen GLCM imaging data for variable screening of SLM prediction models.Inverse difference,mean sum,sum entropy,sum variance,sum of squares,energy,and difference variance were listed as candidate variables,and the prediction efficiency(area under the curve)of the subsequent RFM in the training set and internal validation set was 0.917[95%confidence interval(95%CI):0.866-0.968]and 0.09(95%CI:0.858-0.960),respectively.CONCLUSION A predictive model combining GLCM image features with machine learning can predict SLM in CRC.This model can assist clinicians in making timely and personalized clinical decisions.展开更多
BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combinat...BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.展开更多
BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained...BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.展开更多
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
基金supported by the National Natural Science Foundation of China Fund Project(82272956).
文摘Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.
基金supported by National Health Commission Key Laboratory of Gastrointestinal Tumour Diagnosis and Treatment 2022 Master/Postdoctoral Fund Project(NHCDP2022005)Gansu Provincial Science and Technology Department Joint Scientific Research Fund Project(23JRRA1545)+1 种基金Gansu Provincial Hospital Intra-Hospital Research Fund Project(22GSYYD-37)International Co-Operation Project of Gansu Provincial Science and Technology Department(No.20YF8WA096).
文摘Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.
基金Hainan Clinical Medical Center Construction Project(2021)Excellent Talent Team of Hainan Province(No.QRCBT202121)Key R&D Program of Hainan Province(No.ZDYF2022SHFZ109)。
文摘Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.
文摘BACKGROUND Metastatic colorectal cancer(mCRC)is a common malignancy whose treatment has been a clinical challenge.Cancer-specific survival(CSS)plays a crucial role in assessing patient prognosis and treatment outcomes.However,there is still li-mited research on the factors affecting CSS in mCRC patients and their corre-lation.AIM To predict CSS,we developed a new nomogram model and risk grading system to classify risk levels in patients with mCRC.METHODS Data were extracted from the United States Surveillance,Epidemiology,and End Results database from 2018 to 2023.All eligible patients were randomly divided into a training cohort and a validation cohort.The Cox proportional hazards model was used to investigate the independent risk factors for CSS.A new nomogram model was developed to predict CSS and was evaluated through internal and external validation.RESULTS A multivariate Cox proportional risk model was used to identify independent risk factors for CSS.Then,new CSS columns were developed based on these factors.The consistency index(C-index)of the histogram was 0.718(95%CI:0.712-0.725),and that of the validation cohort was 0.722(95%CI:0.711-0.732),indicating good discrimination ability and better performance than tumor-node-metastasis staging(C-index:0.712-0.732).For the training set,0.533,95%CI:0.525-0.540;for the verification set,0.524,95%CI:0.513-0.535.The calibration map and clinical decision curve showed good agreement and good potential clinical validity.The risk grading system divided all patients into three groups,and the Kaplan-Meier curve showed good stratification and differentiation of CSS between different groups.The median CSS times in the low-risk,medium-risk,and high-risk groups were 36 months(95%CI:34.987-37.013),18 months(95%CI:17.273-18.727),and 5 months(95%CI:4.503-5.497),respectively.CONCLUSION Our study developed a new nomogram model to predict CSS in patients with synchronous mCRC.In addition,the risk-grading system helps to accurately assess patient prognosis and guide treatment.
文摘BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as albumin bilirubin(ALBI)score,liver function index,and carcinoembryonic antigen(CEA)have shown some potential in the prediction of liver metastasis but have not been fully explored.AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI,liver function index,and CEA,and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months.According to the follow-up results,the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1.The risk factors for liver metastasis in patients with CRC were analyzed,a prediction model was constructed by least absolute shrinkage and selection operator(LASSO)logistic regression,internal validation was performed by the bootstrap method,the reliability of the prediction model was evaluated by subject-work characteristic curves,calibration curves,and clinical decision curves,and a column graph was drawn to show the prediction results.RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria.Through LASSO regression variable screening and logistic regression analysis.The ALBI score,alanine aminotransferase(ALT),and CEA were found to be independent predictors of liver metastases in CRC patients[odds ratio(OR)=8.062,95%confidence interval(CI):2.545-25.540],(OR=1.037,95%CI:1.004-1.071)and(OR=1.025,95%CI:1.008-1.043).The area under the receiver operating characteristic curve(AUC)for the combined prediction of CRLM in the modeling group was 0.921,with a sensitivity of 78.0%and a specificity of 95.0%.The H-index was 0.921,and the H-L fit curve hadχ^(2)=0.851,a P value of 0.654,and a slope of the calibration curve approaching 1.This indicates that the model is extremely accurate,and the clinical decision curve demonstrates that it can be applied effectively in the real world.We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method.The AUC was 0.913,while the accuracy was 0.869 and the kappa consistency was 0.709.The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918,sensitivity of 85.0%,specificity of 95.6%,C-index of 0.918,and an H-L fitting curve withχ^(2)=0.586,P=0.746.CONCLUSION The ALBI score,ALT level,and CEA level have a certain value in predicting liver metastasis in patients with CRC.These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC.The risk prediction model developed in this work shows great potential for practical application.
文摘BACKGROUND Synchronous liver metastasis(SLM)is a significant contributor to morbidity in colorectal cancer(CRC).There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC.AIM To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix(GLCM)features collected from magnetic resonance imaging(MRI).METHODS Our study retrospectively enrolled 392 patients with CRC from Yichang Central People’s Hospital from January 2015 to May 2023.Patients were randomly divided into a training and validation group(3:7).The clinical parameters and GLCM features extracted from MRI were included as candidate variables.The prediction model was constructed using a generalized linear regression model,random forest model(RFM),and artificial neural network model.Receiver operating characteristic curves and decision curves were used to evaluate the prediction model.RESULTS Among the 392 patients,48 had SLM(12.24%).We obtained fourteen GLCM imaging data for variable screening of SLM prediction models.Inverse difference,mean sum,sum entropy,sum variance,sum of squares,energy,and difference variance were listed as candidate variables,and the prediction efficiency(area under the curve)of the subsequent RFM in the training set and internal validation set was 0.917[95%confidence interval(95%CI):0.866-0.968]and 0.09(95%CI:0.858-0.960),respectively.CONCLUSION A predictive model combining GLCM image features with machine learning can predict SLM in CRC.This model can assist clinicians in making timely and personalized clinical decisions.
文摘BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.
基金Supported by National Natural Science Foundation of China,No.82260785.
文摘BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.
