The Expression And Prognosis Of Preoperative Peripheral Blood Markers In Four Molecular Subgroups Medulloblastoma

Part ?Clinical characteristics and prognosis of four molecular subgroups of 183 cases medulloblastomaObjectiveMedulloblastoma(MB)is divided into four molecular subgroups including WNT,SHH,Group 3 and Group 4.The prognosis of the WNT MB was the best,the prognosis of the SHH and Group 4 MB were moderated,and the Group 3 MB had the worst prognosis.Nano String-based analysis is a fast,reliable,repeatable and economical MB molecular subgroups classification method compared to other methods.At present,there is no systematic study on the clinical features and prognosis of four molecular subgroups in the Chinese population.This study aimed to investigate the clinical and prognostic characteristics of MB molecular subgroups(WNT,SHH,Group 3 and Group 4)in large sample populations in China.MethodsThis study retrospectively analyzed 183 patients with MB in the First Affiliated Hospital of Zhengzhou University from January 2009 to January 2018.The Nano String-based method was used to detect the molecular classification of tumor samples,and 125 patients were successfully followed up.Clinical data such as gender,age,preoperative KPS score,resection range,tumor location,postoperative radiotherapy(RT)and postoperative chemotherapy(CHT)were collected from the medical records.Follow-up data were obtained through outpatient records or telephone follow-up.The overall survival rate(OS)was defined as the time interval from surgery to death or end of follow-up.Progression-free survival(PFS)was measured from the date of diagnosis to the onset of disease recurrence,death,or final follow-up.Statistical analysis was performed using SPSS 21.0(IBM Crop,Armonk,NY,USA)and X-Tile 3.6.1(http://medicine.yale.edu/lab/rimm/research/software.aspx).Survival curves of progression-free survival(PFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Log-rank test(univariate analysis)was used to compare the survival rates of different groups.To correct multiple comparisons,a Bonferroni adjusted P value was used in these analyses as a significance threshold.Independent prognostic factors(multivariate analysis)were evaluated using a COX proportional hazard regression model.P < 0.05 was defined as statistically significant.Results1.Among 183 MB,Group 3 MB was the most,followed by Group 4 and SHH MB,and WNT MB was the least;WNT MB was significantly lower than SHH in total MB patients and children with MB,Group 3 And Group 4 MB;in terms of tumor location,more than 60% of SHH MB is on the side,but almost all Group 4 MB are in the midline,especially in adult MB;in terms of age distribution,Group 3 MB mainly occurs in 0-9 years old And SHH MB is good for children and adults.WNT and Group 4 MB are most common 3-15 years old.2.In the univariate analysis,the PFS(P = 0.001,P = 0.002)and OS(P = 0.002,P = 0.004)of WNT MB were significantly longer than Group 3 and Group 4 MB.SHH MB's PFS(P = 0.001,P = 0.008)and OS(P = 0.010,P = 0.015)were significantly longer than Group 3 and Group 4 MB.3.In multivariate COX analysis,molecular subgroup was an independent prognostic factor for patients with MB(PFS,P=0.015,OS,P=0.040).Conclusion1.Among 183 MBs,Group 3 MB is the most,followed by Group 4 and SHH MB,with WNT MB being the least,WNT MB is the lowest ratio of men and women,more than 60% of SHH MB is on the side,but almost all Group 4 MB are in the midline,MB is most common in children.2.The prognosis of WNT and SHH MB is better than that of Group 3 and Group 4 MB.3.Molecular subgroups are independent prognostic factors for MB patients.Part ? Expression and prognosis of preoperative peripheral blood markers in four molecular subgroups medulloblastomaObjectivePreoperative peripheral blood markers have been shown to have an impact on the prognosis of a variety of tumors.However,the expression and prognosis of preoperative peripheral blood markers in different molecular subgroups MB have not been reported so far.For the first time,the expression and clinical prognosis of preoperative peripheral blood markers including NLR(neutrophil to lymphocyte ratio),PLR(platelet to lymphocyte ratio),MLR(monocyte to lymphocyte ratio),MPV(mean Platelet distribution volume),PDW(platelet distribution width)and AGR(albumin globulin ratio)in Wingless(WNT),Sonic Hedgehog(SHH),Group 3 and Group 4 MB were studied.MethodsThe study was performed in the first affiliated hospital of Zhengzhou University from January 2009 to January 2018.The postoperative pathological results of 183 patients confirmed with MB.Excluding any patients with potentially inflammatory conditions,39 patients were eventually excluded and 144 patients were enrolled in the cohort.Clinical data were collected from medical records including gender,age,preoperative karnofsky performance status scale(KPS),tumor location,extent of resection,radiotherapy,and chemotherapy.Overall survival(OS)was the interval between surgery and death or end of follow-up,progression-free survival(PFS)was between the date of diagnosis and the date of disease recurrence,death,or final follow-up.The end of the follow-up period was January 1,2019.116 MB patients were successful followed up.Univariate analysis was performed on the clinical prognosis of 116 patients with MB and the four subgroups MB included in them.The Kaplan-Meier method was used to perform survival analysis and plot survival curves.The Log-rank method was used to analyze OS and PFS between patient in different groups.In multivariate analysis,COX regression analysis was used to determine independent prognostic risk factors.One way ANOVA was used to compare the differences in the expression levels of NLR and PLR in WNT,SHH,Group 3 and Group 4 MB,respectively.Results1.Univariate survival analysis showed that PFS(P=0.004,P=0.028)and OS(P<0.001,P=0.003)in patients with low NLR and PLR were significantly longer than those in high NLR and PLR groups.2.One way ANOVA showed that the NLR in Group 3 MB was significantly higher than that of WNT(P<0.01),SHH(P<0.05)MB.The PLR in Group 3(P<0.05)and Group 4(P<0.05)MB was significantly higher than that in WNT MB.3.Univariate survival analyzed the expression levels of NLR and PLR in WNT,SHH,Group 3 and Group 4 MB,respectively.The results revealed that low NLR(P=0.032)in Group 3 MB predicted better OS than that of high NLR group.In Group 4 MB,the OS of low NLR(P=0.027)was significantly longer than that of the high NLR group.The OS(P=0.009)and PFS(P=0.012)in low PLR group was significant longer than that of the high PLR group in Group 4 MB.4.Multivariate survival analysis showed that high NLR and PLR were independent risk factors for predicting prognosis in patients with MB(PFS,P=0.029,OS,P=0.005,OS,P=0.012).Conclusion1.The higher of preoperative NLR and PLR,the worse prognosis of patients with MB.2.Preoperative NLR in Group 3 MB was significantly higher than those in WNT,SHH MB.The preoperative PLR in Group 3 and Group 4 MB were significantly higher than that in WNT MB.3.The increase of preoperative NLR predicted worse prognosis in Group 3 MB.The increase of preoperative NLR and PLR predicted worse prognosis in Group 4 MB.4.Preoperative NLR and PLR are independent prognostic risk factors for the patients with MB.5.Our results suggest that NLR and PLR may be potential prognostic markers for patients with MB.Preoperative NLR and PLR primarily affect the prognosis of Group 3 and Group 4 MB.