1.Association of preoperative plasma fibrinogen levels with adverse outcomes 1 year after endovascular revascularization in diabetes complicated with lower extremity arteriosclerosis obliterans
Yuanyuan DU ; Qingfeng WU ; Lan LI ; Cong LU ; Jingxuan WANG ; Junbo ZHANG ; Qingbin ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):463-471
Objective To explore the impact of preoperative fibrinogen levels on the 1-year adverse outcomes after endovascular revascularization in patients with diabetes complicated with lower extremity arteriosclerosis obliterans(LEASO).Methods We collected the baseline clinical data of 289 patients with diabetes complicated with LEASO,who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to December 2022 for endovascular revascularization.All patients were followed up for 13 to 24 months after interventional therapy,with the follow-up information including major adverse cardiovascular events(MACEs)such as all-cause death,acute myocardial infarction and acute stroke,as well as major adverse lower extremity events(MALEs)such as rest pain in the lower extremities,ulcers or skin defects,gangrene,reocclusion and amputation.A multivariable Cox regression model was used to analyze the related risk factors for adverse outcomes 1 year after endovascular revascularization in patients with diabetes complicated with LEASO,and receiver operating characteristic(ROC)curves were constructed to evaluate the predictive efficacy and optimal cutoff value of fibrinogen levels for endpoint events,and Kaplan-Meier survival curves were drawn.Sensitivity analysis was made to assess the differences in the impact of fibrinogen on endpoint events across various subgroups.Results We recruited a total of 289 patients(55 patients in MACEs and 234 in non-MACEs;68 patients in MALEs and 221 in non-MALEs),with a mean age of 67.6±9.3 years,including 215 males.Multivariate Cox regression analysis showed that elevated plasma fibrinogen was an independent risk factor for MACEs(HR=1.250,95%CI:1.053-1.484,P=0.011)and all-cause death(HR=1.297,95%CI:1.030-1.633,P=0.027)in the cohort followed up 1 year after interventional therapy,but had no significant impact on the occurrence of MALEs(P=0.625).Baseline plasma fibrinogen level 4.32 g/L was the optimal cutoff value for predicting MACEs(sensitivity=0.673,95%CI:0.582-0.767;specificity=0.688,95%CI:0.562-0.775)and all-cause death(sensitivity=0.679,95%CI:0.483-0.880;specificity=0.651,95%CI:0.465-0.755).The AUC for predicting MACEs and all-cause death after interventional therapy was 0.652(95%CI:0.564 2-0.739 1)and 0.619(95%CI:0.507-0.733),respectively.After a median follow-up of 14.03 months,patients with preoperative fibrinogen level ≥ 4.32 g/L had a significantly higher risk of MACEs and all-cause death compared to patients with preoperative fibrinogen<4.32 g/L(P<0.001),and there were no significant differences in different subgroups,including gender(male/female,interaction P=0.836),age(<65 years/≥65 years,interaction P=0.211),smoking status(never smoked/current or former smoker,interaction P=0.779),chronic kidney disease(yes/no,interaction P=0.360),and heart failure(yes/no,interaction P=0.114).Conclusion Preoperative plasma fibrinogen≥4.32 g/L is an effective indicator for predicting MACEs and all-cause mortality following endovascular revascularization in patients with diabetes and LEASO.
3.Correlation analysis of lipid metabolism index,serum γ-glutamyltranspeptidase and coronary heart disease complicated with coronary calcification
Xueqi LI ; Shiguang LI ; Enwen XU ; Ruilei ZHANG ; Pengli CHEN ; Qingbin ZHANG
Tianjin Medical Journal 2025;53(11):1165-1169
Objective To analyze the correlation between lipid metabolism indexes,serum gamma-glutamyl transpeptidyase(γ-GGT)and coronary heart disease(CHD)complicated with coronary artery calcification(CAC).Methods A total of 300 CHD patients admitted in this study were divided into the CAC group(n=193)and the non-CAC group(n=107).Clinical data of the two groups were compared,including high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triglyceride(TG),Apolipoprotein A1(Apo-A1),Apo-B(APO-B)and γ-GGT.The influencing factors of CAC were analyzed by multiple Logistic factors.And a nomogram prediction model was established.Results The basic data of the two groups were compared.Patients of the CAC group was older,had higher proportion of patients with hypertension and diabetes,had higher levels of LDL-C,TC,Apo-B and γ-GGT and lower level of Apo-A1 than those of the non-CAC group(P<0.05).The results of Logistic multivariate regression analysis showed that advanced age,combined history of diabetes,elevated LDL-C,TC,Apo-B and γ-GGT were risk factors of CHD complicated with CAC,while elevated Apo-A1 was the protective factor of CHD complicated with CAC(P<0.05).The AUC of the constructed nomogram model was 0.880(95%CI:0.840-0.919),which showed good distinguishing ability.Conclusion CHD complicated with CAC is related to lipid metabolism and γ-GGT level.The nomogram model constructed based on influencing factors can be used for clinical early warning of CAC risk.
4.Proximal pericolic lymph node metastasis beyond 10 cm in rectal cancer: patterns of prognostic impact of extended resection in a prospective cohort study
Xuyang YANG ; Yang ZHANG ; Lina YE ; Qingbin WU ; Tinghan YANG ; Mingtian WEI ; Xiangbing DENG ; Haining CHEN ; Wenjian MENG ; Ziqiang WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1015-1025
Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.
5.Mediating effects of self-management and medication adherence between type D personality and viral load in HIV-infected individuals
Yanping JI ; Qingbin DING ; Tianyi BU ; Kun WANG ; Xue WANG ; Jing ZHANG
Chinese Journal of Modern Nursing 2025;31(4):514-519
Objective:To explore the mediating effects of self-management and medication adherence between type D personality and viral load in HIV-infected individuals.Methods:HIV patients who were newly diagnosed and undergoing antiretroviral therapy (ART) at the Heilongjiang AIDS Treatment Center of the Fourth Hospital of Harbin Medical University from October 2023 to March 2024 were enrolled by convenience sampling. Data were collected using the Type D Personality Scale-14 (DS-14), HIV Self-Management Scale (HIVSMS), and 8-item Morisky Medication Adherence Scale (MMAS-8). HIV-1 viral load was also measured. Pearson correlation analysis explored the relationships among type D personality, self-management, medication adherence, and viral load. The SPSS Process V4.0 macro was used to test the mediating effects.Results:A total of 318 questionnaires were distributed and 313 valid responses were collected (effective response rate: 98.43%). The mean scores for the 313 HIV-infected individuals were as follows: DS-14 (33.39±4.98), HIVSMS (29.84±4.41), and MMAS-8 (6.11±1.29). The mean viral load was (1 803.19±870.81) copies/ml. Pearson correlation analysis showed that type D personality was negatively correlated with self-management and medication adherence ( r=-0.307, -0.208, respectively; P<0.01) and positively correlated with viral load ( r=0.213; P<0.01). Medication adherence was negatively correlated with viral load ( r=-0.232; P<0.01), while self-management was positively correlated with medication adherence ( r=0.353; P<0.01). The mediation analysis revealed that self-management and medication adherence played a chain mediating role between type D personality and viral load, with a mediation effect value of 0.016, accounting for 8.08% of the total effect. Conclusions:Type D personality directly influences the viral load of HIV-infected individuals and indirectly affects it through the mediating effects of self-management and medication adherence.
6.Association of preoperative plasma fibrinogen levels with adverse outcomes 1 year after endovascular revascularization in diabetes complicated with lower extremity arteriosclerosis obliterans
Yuanyuan DU ; Qingfeng WU ; Lan LI ; Cong LU ; Jingxuan WANG ; Junbo ZHANG ; Qingbin ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):463-471
Objective To explore the impact of preoperative fibrinogen levels on the 1-year adverse outcomes after endovascular revascularization in patients with diabetes complicated with lower extremity arteriosclerosis obliterans(LEASO).Methods We collected the baseline clinical data of 289 patients with diabetes complicated with LEASO,who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to December 2022 for endovascular revascularization.All patients were followed up for 13 to 24 months after interventional therapy,with the follow-up information including major adverse cardiovascular events(MACEs)such as all-cause death,acute myocardial infarction and acute stroke,as well as major adverse lower extremity events(MALEs)such as rest pain in the lower extremities,ulcers or skin defects,gangrene,reocclusion and amputation.A multivariable Cox regression model was used to analyze the related risk factors for adverse outcomes 1 year after endovascular revascularization in patients with diabetes complicated with LEASO,and receiver operating characteristic(ROC)curves were constructed to evaluate the predictive efficacy and optimal cutoff value of fibrinogen levels for endpoint events,and Kaplan-Meier survival curves were drawn.Sensitivity analysis was made to assess the differences in the impact of fibrinogen on endpoint events across various subgroups.Results We recruited a total of 289 patients(55 patients in MACEs and 234 in non-MACEs;68 patients in MALEs and 221 in non-MALEs),with a mean age of 67.6±9.3 years,including 215 males.Multivariate Cox regression analysis showed that elevated plasma fibrinogen was an independent risk factor for MACEs(HR=1.250,95%CI:1.053-1.484,P=0.011)and all-cause death(HR=1.297,95%CI:1.030-1.633,P=0.027)in the cohort followed up 1 year after interventional therapy,but had no significant impact on the occurrence of MALEs(P=0.625).Baseline plasma fibrinogen level 4.32 g/L was the optimal cutoff value for predicting MACEs(sensitivity=0.673,95%CI:0.582-0.767;specificity=0.688,95%CI:0.562-0.775)and all-cause death(sensitivity=0.679,95%CI:0.483-0.880;specificity=0.651,95%CI:0.465-0.755).The AUC for predicting MACEs and all-cause death after interventional therapy was 0.652(95%CI:0.564 2-0.739 1)and 0.619(95%CI:0.507-0.733),respectively.After a median follow-up of 14.03 months,patients with preoperative fibrinogen level ≥ 4.32 g/L had a significantly higher risk of MACEs and all-cause death compared to patients with preoperative fibrinogen<4.32 g/L(P<0.001),and there were no significant differences in different subgroups,including gender(male/female,interaction P=0.836),age(<65 years/≥65 years,interaction P=0.211),smoking status(never smoked/current or former smoker,interaction P=0.779),chronic kidney disease(yes/no,interaction P=0.360),and heart failure(yes/no,interaction P=0.114).Conclusion Preoperative plasma fibrinogen≥4.32 g/L is an effective indicator for predicting MACEs and all-cause mortality following endovascular revascularization in patients with diabetes and LEASO.
7.Correlation analysis of lipid metabolism index,serum γ-glutamyltranspeptidase and coronary heart disease complicated with coronary calcification
Xueqi LI ; Shiguang LI ; Enwen XU ; Ruilei ZHANG ; Pengli CHEN ; Qingbin ZHANG
Tianjin Medical Journal 2025;53(11):1165-1169
Objective To analyze the correlation between lipid metabolism indexes,serum gamma-glutamyl transpeptidyase(γ-GGT)and coronary heart disease(CHD)complicated with coronary artery calcification(CAC).Methods A total of 300 CHD patients admitted in this study were divided into the CAC group(n=193)and the non-CAC group(n=107).Clinical data of the two groups were compared,including high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triglyceride(TG),Apolipoprotein A1(Apo-A1),Apo-B(APO-B)and γ-GGT.The influencing factors of CAC were analyzed by multiple Logistic factors.And a nomogram prediction model was established.Results The basic data of the two groups were compared.Patients of the CAC group was older,had higher proportion of patients with hypertension and diabetes,had higher levels of LDL-C,TC,Apo-B and γ-GGT and lower level of Apo-A1 than those of the non-CAC group(P<0.05).The results of Logistic multivariate regression analysis showed that advanced age,combined history of diabetes,elevated LDL-C,TC,Apo-B and γ-GGT were risk factors of CHD complicated with CAC,while elevated Apo-A1 was the protective factor of CHD complicated with CAC(P<0.05).The AUC of the constructed nomogram model was 0.880(95%CI:0.840-0.919),which showed good distinguishing ability.Conclusion CHD complicated with CAC is related to lipid metabolism and γ-GGT level.The nomogram model constructed based on influencing factors can be used for clinical early warning of CAC risk.
8.Proximal pericolic lymph node metastasis beyond 10 cm in rectal cancer: patterns of prognostic impact of extended resection in a prospective cohort study
Xuyang YANG ; Yang ZHANG ; Lina YE ; Qingbin WU ; Tinghan YANG ; Mingtian WEI ; Xiangbing DENG ; Haining CHEN ; Wenjian MENG ; Ziqiang WANG
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1015-1025
Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.
9.Mediating effects of self-management and medication adherence between type D personality and viral load in HIV-infected individuals
Yanping JI ; Qingbin DING ; Tianyi BU ; Kun WANG ; Xue WANG ; Jing ZHANG
Chinese Journal of Modern Nursing 2025;31(4):514-519
Objective:To explore the mediating effects of self-management and medication adherence between type D personality and viral load in HIV-infected individuals.Methods:HIV patients who were newly diagnosed and undergoing antiretroviral therapy (ART) at the Heilongjiang AIDS Treatment Center of the Fourth Hospital of Harbin Medical University from October 2023 to March 2024 were enrolled by convenience sampling. Data were collected using the Type D Personality Scale-14 (DS-14), HIV Self-Management Scale (HIVSMS), and 8-item Morisky Medication Adherence Scale (MMAS-8). HIV-1 viral load was also measured. Pearson correlation analysis explored the relationships among type D personality, self-management, medication adherence, and viral load. The SPSS Process V4.0 macro was used to test the mediating effects.Results:A total of 318 questionnaires were distributed and 313 valid responses were collected (effective response rate: 98.43%). The mean scores for the 313 HIV-infected individuals were as follows: DS-14 (33.39±4.98), HIVSMS (29.84±4.41), and MMAS-8 (6.11±1.29). The mean viral load was (1 803.19±870.81) copies/ml. Pearson correlation analysis showed that type D personality was negatively correlated with self-management and medication adherence ( r=-0.307, -0.208, respectively; P<0.01) and positively correlated with viral load ( r=0.213; P<0.01). Medication adherence was negatively correlated with viral load ( r=-0.232; P<0.01), while self-management was positively correlated with medication adherence ( r=0.353; P<0.01). The mediation analysis revealed that self-management and medication adherence played a chain mediating role between type D personality and viral load, with a mediation effect value of 0.016, accounting for 8.08% of the total effect. Conclusions:Type D personality directly influences the viral load of HIV-infected individuals and indirectly affects it through the mediating effects of self-management and medication adherence.
10.Interaction analysis of mismatch repair protein and adverse clinicopathological features on prognosis of colon cancer
Kexuan LI ; Fuqiang ZHAO ; Qingbin WU ; Junling ZHANG ; Shuangling LUO ; Shidong HU ; Bin WU ; Heli LI ; Guole LIN ; Huizhong QIU ; Junyang LU ; Lai XU ; Zheng WANG ; Xiaohui DU ; Liang KANG ; Xin WANG ; Ziqiang WANG ; Qian LIU ; Yi XIAO
Chinese Journal of Digestive Surgery 2024;23(6):826-835
Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

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