The Relationship Between PLR,NLR And LWR In Peripheral Blood Before Neoadjuvant Chemotherapy Of Initial Resectable Colorectal Cancer With Liver Metastases And Chemotherapy Efficacy And Tumor Prognosis

Background and purpose:Globally,incidence of colorectal cancer(CRC)ranks first among gastrointestinal malignancies.At the same time,it is also the most common cause of loss of life for cancer patients.The liver serves as a communication hub connecting the portal vein and the vena cavasystem.Because it has the function of filtering blood,CRC is often the first to transfer to the liver through the blood.For patients with colorectal cancer liver metastasis(CRLM),complete surgical resection is an effective treatment that can be potentially cured.Neoadjuvant chemotherapy(NAC)can not only improve the surgical resection rate of CRLM patients,and can effectively extend its survival time.However,the effective rate of neoadjuvant chemotherapy is only about 50%.At the same time,NAC not only benefits patients,but also increases the incidence of patient adverse reactions,such as chronic intestinal dysfunction,bone marrow suppression,leukopenia,anemia,thrombocytopenia,etc.Which patients can benefit from NAC?Is the effect of NAC on bone marrow suppression related to prognosis?Does NAC affect the number and function of inflammatory cells in peripheral blood and tumor tissue?Whether the dominant population of colorectal cancer patients with NAC can be screened out by peripheral blood or relatively simple methods is a question that clinicians have been working hard to explore.In addition,tumor invasion and migration are inseparable from inflammation.Systemic inflammation has been considered an important part of the tumor immune microenvironment and plays an indispensable role in the occurrence and development of many solid tumors,such as neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),lymphocyte-to-white blood cell ratio(LWR)and colorectal cancer related to poor prognosis.NLR,PLR,and LWR mainly represent a dynamic change process among neutrophils,white blood cells,lymphocytes and platelets in the body,through which it can reflect the severity of the body’s inflammatory response and the body’s anti-tumor immune status.However,the levels of NLR,PLR and LWR in the peripheral blood have relatively few studies on the prediction of the curative effect of NAC in patients with liver metastasis of colorectal cancer and its influence on the prognosis.In clinical practice,targeted drug therapy for patients with metastatic colorectal cancer has greatly improved the patient’s quality of life and effectively prolonged survival time.Performing KRAS,NRAS and BRAF gene detection on cancer patients in the clinic can more accurately guide the individualized targeted therapy for patients with liver metastases from colorectal cancer.Therefore,the first purpose of this study is to discuss whether the levels of PLR,NLR,and LWR in peripheral blood can predict the efficacy of NAC and whether it is related to the patient’s prognosis.The second purpose is to explore whether KRAS,NRAS and BRAF gene mutations are related to PLR,NLR and LWR.Method:We selected patients with initially resectable colorectal cancer liver metastases who received neoadjuvant chemotherapy(NAC)from the General Surgery Department of the Affiliated Cancer Hospital of Zhengzhou University from January2015 to December 2016,and collected clinical data,such as age,gender,primary tumor location,degree of differentiation,clinical stage,lymph node metastasis,chemotherapy regimen,and follow-up survival time of patients before NAC.At the same time,the results of routine peripheral blood tests and tumor markers before NAC were collected,and the values of PLR,NLR and LWR were calculated.By making the receiver operating characteristic(ROC)curve,the Youden index was calculated,and the best cut-off values of PLR,NLR and LWR were judged according to the maximum value of the Youden index.Then according to the size of the best cut-off value,PLR,NLR and LWR were divided into high value group(>cut-off value)and low value group(≤cut-off value).In addition,the complete test result data of KRAS,NRAS and BRAF gene mutations of all patients were collected.The independent sample t-test and theχ~2-test method were used to analyze the correlation between the levels of PLR,NLR and LWR before NAC and clinical features,efficacy and prognosis.In addition,this test method was used to analyze the correlation between KRAS,NRAS and BRAF gene mutations and clinicopathological parameters,as well as PLR,NLR and LWR.The Kaplan-Meier method was used to establish a patient’s survival curve and perform Log-rank test on it.Univariate analysis was performed by Logistic regression method.At the same time,multivariate analysis was performed by COX regression method.Result:A total of 197 patients were eligible for selection in this study.Through the ROC curve,it was found that the area under the curve of LWR was less than 50%,so we excluded it as a research indicator.By making the ROC curve,we calculated that the best cut-off values of PLR and NLR were 148.84 and 2.17,respectively.The area,sensitivity and specificity of PLR and NLR under this curve were 0.680,65.7%,66.3%and 0.767,75.5%,64.2%.In terms of patient gender,age,lymph node metastasis and degree of differentiation,the PLR and NLR of the high-value group were compared with those of the low-value group,respectively,and there was no comparison between the two groups(P>0.05).However,there was a certain correlation between the PLR and NLR values and the location of the primary tumor(P<0.05).In terms of gender,age,primary tumor location,lymph node metastasis,degree of differentiation,etc.,the mutation rates of KRAS and NRAS genes had no correlation with the above clinicopathological parameters(P>0.05).There was no significant difference in the BRAF gene mutation rate in terms of age,primary tumor location,lymph node metastasis,degree of differentiation and other clinicopathological characteristics(P>0.05).In terms of gender,the BRAF gene mutation rate in female patients was 9.86%(7/71)which was higher than 1.58%(2/126)of males,and there was a significant difference between the two groups(P=0.008).As to lymph node metastasis,KRAS gene mutation rate of patients with positive lymph node metastasis was 52.48%(53/101)significantly higher than that of patients with negative lymph node metastasis,26.04%(25/96),and the two groups had significant differences(P<0.01)).In addition,in terms of white blood cell count,platelet count,lymphocyte count,neutrophil count,PLR and NLR,there was no statistical difference between wild-type KRAS,NRAS and BRAF and mutant KRAS,NRAS and BRAF(P>0.05).Regarding the efficacy of NAC chemotherapy,the remission rate of the low-PLR group was 67.34%(66/98)higher than that of the high-PLR group was 52.53%(52/99),χ~2=4.504,P=0.034,there was a difference between the two groups(P<0.05).The remission rate of the low NLR group was 67.42%(60/89)higher than that of the high NLR group was 59.26%(64/108),χ~2=1.392,P=0.238,there was no significant difference between them(P>0.05).The results of the Kaplan-Meier curve showed that in terms of the OS and DFS of patients,the low PLR and NLR groups were higher than the high PLR and NLR groups,and P values between each group were less than 0.001,which was statistically different.In terms of survival time,the wild-type KRAS gene had a longer life cycle than the mutant group,and there were significant differences between the two groups(χ~2=6.497,P=0.011).Similarly,the wild-type BRAF gene had a longer survival time than the mutant group,and there was a significant difference between the two groups(χ~2=9.172,P=0.003).Logistic univariate analysis results showed that the primary tumor location,degree of differentiation,lymph node metastasis,platelet count(≥300×10~9),neutrophil count(≥6.02×10~9),high PLR,high NLR,KRAS mutant,NRAS mutant and BRAF mutant were all related to the poor prognosis of patients with liver metastases from colorectal cancer,and the difference was statistically significant(P<0.05).In COX multivariate analysis,elevated PLR and NLR were independent risk factors for the poor prognosis of CRLM patients(P<0.001).In addition,KRAS mutations,NRAS mutations and BRAF mutations were also independent factors influencing the poor prognosis of CRLM patients(P<0.05).Conclusion:1.In terms of the results of this study,PLR and NLR can be used as clinical indicators to predict the prognosis of CRLM patients.2.The increase of PLR and NLR before NAC was an independent risk factor affecting the prognosis of CRLM patients.3.There was no significant correlation between the values of PLR and NLR and KRAS,NRAS and BRAF.