| Objective: To analyze the expression of Neutrophil-to-lymphocyte ratio(NLR),Platelet-to lymphocyte ratio(PLR)and Systemic immune-inflammation index(SII)in GEP-NEN,and to study their relationship with the clinical characteristics of gastroenteropancreatic neuroendocrine tumor(GEP-NEN).To explore its value as well as possible factors on the prognosis of GEP-NEN furthermore.Methods: The clinical data of patients with pathological diagnosis of GEP-NEN in Qingdao University Affiliated Hospital from November 2012 to December 2018 were collected.Data was collected and followed up for the included patients,and the relationship between clinical features,diagnostic and prognosis value were analyzed.The last blood routine results of patients before treatment were collected and used to calculate NLR,PLR,SII values.Using receiver operating characteristic(ROC)curve to calculate NLR,PLR,SII optimal cut-off value,with the optimal cut-off value as the limit to divide into high-value group and the low-value group.The relationship between inflammation-related factors and clinicopathological indicators was analyzed.The KM curve was drawn and Log-rank tests were performed,and Cox regression was used for univariate and multivariate survival analysis,and the meaningful results were included in the Cox proportional hazards model.Results:(1)A total of 214 patients with GEP-NENs were screened.The male-to-female ratio of 1.52:1 with 85 were female(39.7%)and 129 were male(60.3%).The average age at diagnosis was 59.89±12.29 years old,and the median age at diagnosis was 60 years old.(2)Clinical symptoms included hypoglycemia in 6 patients(2.8%),diarrhea in 28 patients(13.1%),abdominal pain in 81 patients(37.9%),gastrointestinal bleeding in 24 patients(11.2%),jaundice in 1 patient(0.5%),and asymptomatic in 41 patient(19.2%).(3)There were 117 cases(54.7%)with G1,35 cases(16.4%)with G2,19 cases(8.9 %)with G3,16cases(7.5%)with Mi NEN,and 27 cases(12.6%)with NEC.(4)There were 57 patients(26.6%)with gastric NEN,104(68.6%)with intestinal NEN,and 53(24.8%)with pancreatic NEN.Pancreatic NEN had a 29.5% probability of metastasis at grade G1/G2,which was higher than that of gastrointestinal NEN.64.9% of gastric NEN patients were grade G3 or NEC.(5)The immune marker chromoprotein A(CGA)was positive in 126cases(58.9%),and synaptophysin(SYN)was positive in 196 cases(91.6%).The expression of CGA in different pathological grades had statistical difference(P<0.05).(6)Draw the ROC curve of the Ki67 index,and get 10% as the best cut-off value for grouping.In the Ki67>10% group,the proportion of age>60 years,male,lymph node metastasis,distant metastasis,G3 and above grade,poor differentiation,tumor diameter tumor size of≥2.5cm was more(P<0.05).(7)Kruskal-Wallis H test showed that the distribution of NLR,PLR and SII were different in pathological grades and primary disease sites,and the differences were statistically significant(P<0.05).(8)The ROC curves of NLR,PLR and SII were drawn to obtain the best cut-off value for grouping.There were 79 patients(36.9%)with NLR>3.99,135 patients(63.1%)with NLR≤3.99;97 patients(45.3%)with PLR>147.23,117 patients(54.7%)with PLR≤147.23;103 patients(48.1%)with SII>644.00,111 patients(51.9%)with SII≤644.00.There were significant differences in risk factors such as tumor diameter,primary site,pathological grade,vascular invasion,nerve invasion,lymph node metastasis,and distant metastasis between the high value groups and low value groups(P<0.05).(9)Logistic regression analysis to explore the relationship between NLR,PLR,SII and Ki67 and prognosis of GEP-NEN.The area under the ROC curve(AUC)calculated by the combined index of SII and Ki67 was equal to 0.857,which was greater than the AUC of a single inflammation-related factor.(10)As the last follow-up,145 patients(75.3%)survived and 69(24.7%)died.The follow-up time ranged from 1 to 107 months.The median follow-up time was 47 months,and the mean follow-up time was 44.66 months.(11)Univariate analysis showed that there were no statistically significant differences in the survival curves of smoking history,drinking history,family tumor history,and CGA,while gender,age,Ki67 grouping,lymph node metastasis,vascular invasion,neural invasion,distant metastasis,NLR,PLR,SII,degree of differentiation,pathological grade,location of disease and other factors were related to the prognosis of patients(P<0.05).(12)The stepwise regression method was selected for multivariate Cox regression analysis.The results showed that Ki67>10%,NLR>3.99 and poor differentiation were independent risk factors affecting the survival and prognosis of GEP-NEN patients.Conclusion: 1.There are differences in the distribution of NLR,PLR and SII in different pathological grades and disease sites.The high value groups have characteristics of advanced age,poor differentiation and accompanying metastasis.2.Survival analysis showed that NLR,PLR and SII could evaluate the prognosis of GEP-NEN patients,and NLR was an independent risk factor affecting the prognosis of GEP-NEN patients.3.Ki67index>10% is related to the prognosis of patients,and the combination of Ki67 index and SII has better prognosis evaluation value for GEP-NEN patients.4.Multivariate Cox regression analysis showed that Ki67>10%,poor differentiation and NLR>3.99 were independent risk factors affecting the survival and prognosis of GEP-NEN patients. |
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