| Background and Objective: Colorectal cancer is one of the most common malignant tumors in clinic,and the incidence and mortality rates are continually increasing worldwide.The main cause of death is distant metastasis.During the development of colorectal cancer,about 25% of patients with concurrent liver metastases and 50%-60% of the patients will develop synchronous liver metastasis.Liver resection is the only treatment strategy that may lead to long-term survival and even cure for patients with CRLM.About 50% of CRLM patients had intrahepatic recurrent or distant metastasis within 2 years after liver resection,and didn't significantly prolonged survival time.Therefore,preoperative evaluation of postoperative recurrence and survival prognosis of CRLM can help select appropriate patients for surgical treatment.It can provide reference for patients with poor surgical treatment,and can maximize the survival benefit of patients undergoing surgery.It can accurately predict postoperative recurrence and survival condition in CRLM patients prediction system,which can be used as a selection of CRLM patients and postoperative adjuvant therapy strategy of reference.There are multiple scoring system for predicting CRLM postoperative recurrence and survival.Prediction system is the most widely clinical risk factors scoring system,which in different medical center can appear different predictions.However,neither is there clinical sufficient basis for clinical decision.Molecular risk factor scoring system test procedure is complex and costly,tumor loadscore is only based on the preoperative imaging of liver metastasis on number and diameter to rate.Both have some limitations.Therefore,to explore a prediction system which is easy to operate,objective and accurate index,is still an urgent problem to solve the liver metastasis of colorectal cancer.Studies have identified that inflammation is associated with the progress of most malignant tumors including colorectal cancer.The preoperative systemic inflammatory response is associated with postoperative survival of a variety of tumors.Systemic inflammatory biomarkers and the related scoring system in the prognosis of CRLM also have very good predictive value in assessment.In recent years,some scholars put forward to use immune grading technology to focus on tumor tissue features in the colorectal cancer and conduct digital pathology score in order to predict the patient's life cycle.It is an important progress in tumor immune pathology.Systemic inflammatory score and tumor immunoscore adopted by the technology in the clinical applications have been mature.These two technologies have the following characteristics: simple and strong repeatability.This study will explore the survival prognostic effect of systemic inflammatory responsescore and tumor immunoscore on colorectal cancer patients with liver metastases.The risk factor prediction model of systemic inflammatory response combined with tumor immunoscore was established,and the predictive effect of this model was preliminarily tested.Materials and Methods: Object of study: Collected in January 2009 to June 2015,in the First Affiliated Hospital of Guangxi Medical University,were the clinicopathologic data and follow-up data of radical primary tumors and liver metastases resection surgery in patients with synchronous liver metastasis of colorectal cancer.A total of 71 cases were selected,including 48 males and 23 females;age: 23-80,median age: 62.The primary lesion and liver metastasis were simultaneous resected in 48 patients and 23 patients were stages resected.Risk factor: Collected 71 cases of patients with clinicopathologic data and preoperative blood biochemical examination results.According to the results of preoperative blood biochemical examination systemic inflammatory response score on all cases,using modify Glasgow Prognosis Score(mGPS)and preoperative neutrophils/lymphocyte ratio(NLR)as a scoring criteria.In paraffin-embedded specimens from 71 cases of patients with colorectal primary focal tumors and 48 cases of patients without chemotherapy with liver metastases tumors,immunohistochemical detection of tissue samples were collected to immunoscore according to Galon immune scoring method.Using Kplan-Meier method,survival analysis and Cox regression analysis were performed.Single factor analysis and multifactor analysis were carried out to determine the CRLM patients' overall survival and disease-free survival,and the independent risk factors were screened out.Establishment and utility detection of system inflammatory response combined with tumor immune risk factor scoring system: Based on the principle of the higher a risk score is,the worse prognosis the negative predictor will be;the negative predictor is plus point,and the positive predictor is minus point.ROC curve was used to detect thepostoperative survival prediction value of CRLM patients.The results were defined as the low-risk group,and the score was greater than 1,which was defined as the high-risk group.Log-rank test was used to compare the overall survival time and disease-free survival time between the two groups.Results: 1.1 The effect of clinicopathologic factors on the postoperative survival prognosis after CRLM The median survival time of the whole group was 40 months and the median survival time was 20 months.The postoperative survival rates of 1?2?3 year were 94.37%,81.10% and 76.81% respectively.The postoperative disease-free survival rates of 1?2?3 year were 76.81%,49.03% and 35.35% respectively.The results of cox regression analysis showed that: The higher the number of LM,the higher the risk of death and the number of LM.The cox regression analysis results showed that: The higher the number of LM,the higher the risk of death.Each additional LM increased,and then the risk of death increased by 1.32(1.112-1.568)times(P=0.002);The higher the preoperation C-reactive protein(CRP)level,the higher the risk of death(HR=1.192(0.938-1.495),P=0.034).The greater the number of LM,the higher the risk of recurrence(HR=1.276(1.090-1.494),P=0.002).The higher the pre-operation CRP level,the higher the risk of recurrence(1.168(0.915-1.525),P=0.041);The higher the CA199 level,the higher the risk of recurrence(HR=1.001(1-1.002),P=0.006).1.2 The effect of systemic inflammation response score on postoperative survival prognosis of CRLM patients The results of cox regression analysis showed that: mGPS and NLR> 5 were all risk factors for postoperative survival and recurrence of CRLM.The higher the score with the higher the risk of death.Compared to mGPS=0 group,the death risks of mGPS=1 and mGPS=2 were 3.915(1.758-8.721)times and 7.877(3.258-19.043)timesrespectively,and P=0.001 and P<0.001 respectively.The mortality risk of NLR> 5 was 2.987(1.172-7.614)times of NLR?5,P=0.022.The recurrence risks of mGPS=1 and mGPS=2 were 1.69(0.868-3.29)times and 4.762(2.239-10.127)times of the mGPS=0 group respectively,and P=0.123 and P<0.001 respectively.The recurrence risk of NLR>5 was higher than that of NLR?5,HR=3.063(1.401-6.698),and P=0.005.Multiple factors cox regression analysis showed that the independent risk factors for postoperative survival and recurrence were mGPS,while NLR>5 was not an independent risk factor.The death risks of mGPS=1 and mGPS=2 were 4.134(1.819-9.391)times and 9.085(3.201-25.789)times of the mGPS=0 respectively,and P were 0.002 and <0.001 respectively.The recurrence risks of mGPS=1 and mGPS=2 were 1.549(0.78-3.073)times and 5.324(2.01-14.099)times respectively,and P were 0.211 and 0.001 respectively.1.3 The effect of tumor immunoscore on the postoperative survival prognosis of CRLMpatients The results of cox regression analysis showed that: The immunoscore of primary tumor was a risk factor for postoperative survival and recurrence CRLM,and the immunoscore of liver metastasis was not a risk factor.The higher the immunoscore of the primary tumor with the lower the risk of postoperative mortality,and P<0.001.Compared to the primary tumor immunoscore =0,the scores were 1,2,3,4,whose HR were 0.489(0.139-1.721),0.205(0.058-0.728),0.12(0.035-0.405)and 0.056(0.011-0.272)respectively,and P was 0.265,0.014,0.001 and <0.001 respectively.The higher the immunoscore of primary tumor with the lower the risk of recurrence,and P=0.001.Compared to the primary tumor immunoscore=0,the scores were 1,2,3,4,whose HR were 0.452(0.144-1.423),0.192(0.061-0.61),0.141(0.048-0.414)and 0.099(0.028-0.353)respectively,and P was 0.175,0.005,<0.001 and <0.001 respectively.Multiple factors cox regression analysis showed that the independent risk factors for postoperative survival and recurrence were the immunoscore of primary tumor.The higher the immunoscore with the lower the risk of postoperative mortality.Compared to the primary tumor immunoscore =0,the scores were 1,2,3,4,whose mortality risks were 0.619(0.153-2.498),0.282(0.069-1.153),0.156(0.041-0.591)and 0.097(0.017-0.539)respectively,and P was 0.500,0.078,0.006 and 0.008 respectively.The higher the immunoscore of the primary tumor with the lower the risk of postoperative recurrence.Compared to the primary tumor immunoscore =0,the scores were 1,2,3,4,whose risks of postoperative recurrence were 0.312(0.091-1.068),0.159(0.047-0.541),0.136(0.044-0.418)and 0.112(0.028-0.457)respectively,and P was 0.064,0.003,0.001 and 0.002 respectively.1.4 Establishment and utility detection of systematic inflammatory response combined with tumor immunoscore model The above COX multifactor analysis results showed that the independent risk factors affecting the total postoperative survival and disease-free survival of CRLM patients included the number of LM,mGPS score and the immunoscore of primary tumor.Therefore,these three risk factors were put into the score.The formula was:the number of LM + mGPS score-the immunoscore of primary tumor.ROC curve inspection systemic inflammatory response combined with tumor immunorescore predicted that the AUC value of postoperative DFS in CRLM patients was 0.743,and the sensitivity was 69.39% with a specificity of 77.27%.The test results of low and high-risk groups showed that the OS and DFS of low-risk group were significantly better than those in the high-risk group.The difference between the two groups was statistically significant,and P<0.001.Conclusion: 1.The number of LMand CRPlevel in clinicopathological factors was a risk factor affecting the survival of CRLM patients.The number of LM?CRP level and the CA199 level were the risk factors for the postoperative recurrence and metastasis of CRLM patients.2.mGPS score and NLR were both risk factors for postoperative survival and recurrence and metastasis of CRLM patients.However,multivariate analysis showed that only mGPS score was an independent risk factor affecting the postoperative survival and recurrence and metastasis of CRLM patients.3.The immunoscore of primary tumor was a risk factor and independent risk factor affecting the postoperative survival and postoperative recurrence and metastasis of CRLM patients.The immunoscore of metastasis had no effect on thepostoperative survival and recurrence of CRLM patients.4.The test results of ROC curve showed that the systemic inflammation response combined with tumor immunoscore had high accuracy in predicting both OS and DFS in CRLM patients.The systemic inflammation response combined with tumor immunoscore was a low-risk group of CRLM patients whose total survival and disease-free survival were significantly better than those in the high-risk group. |
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