Exploration And Research On The Correlation Between Peripheral Blood Immune-inflammatory Protein Complexes And Breast Cancer

Background and purpose:Breast cancer has the highest incidence rate among malignant tumors in the world.The prediction of prognosis and early detection of tumor progression are always been the focus of research.In recent years,studies have found that serum immunoinflammation-related protein complexes(IIRPCs)have potential value in monitoring tumor development.However,there is no study-on this index in breast cancer patients.Therefore,the purpose of our study is to explore whether the type and level of IIRPCs in serum of breast cancer patients are related to the clinicopathological characteristics of breast cancer.And we also explored whether this index can predict the risk of recurrence and metastasis of hormone receptor positive and HER2 negative breast cancer patients.Method:In the first part,we enrolled patients with triple negative breast cancer,or have four or more involved lymph nodes,or less than 35 years of age at diagnosis,or had metastasis or recurrence.The IIRPCs in peripheral blood was separated by polyacrylamide gel electrophoresis(native-PAGE).Then we used Quantity One software to quantitative analysis the protein band and analyzed the relationship between IIRPCs and the clinicopathological features of breast cancer.In the second part,we selected hormone receptor positive and HER2 negative breast cancer patients to explore whether IIRPCs can predict the risk of recurrence and metastasis.Therefore,we first used the National Cancer Institute's "surveillance,epidemiology and outcome database"(SEER database)to verify the 5-year clinical post-treatment score model(CTS5),which was a prognostic tool established in recent years to assess the risk of late recurrence of breast cancer.Then according to CTS5 scores we divided our hormone receptor positive and HER2 negative breast cancer patient into three groups:low-risk,intermediate risk and high-risk.The type and level of IIRPCs of these patients were detected and analyzed to explore whether IIRPCs can predict the risk of recurrence and metastasis.Result:In the first part,a total of 289 patients were included,of which 84 patients had local recurrence or metastasis.Most of the serum samples were pattern a(123/289,42.6%)and pattern b(108/289,37.4%)of IIRPCs.There was no significant difference in IIRPCs patterns between patients with and without disease progression(p=0.205),as well as between TNBC patients and non TNBC patients(p=0.231).The level of IIRPCs was not related to the histological type,tumor size or lymph node status of breast cancer.However,the protein level of patients with disease progression was significantly higher than that of patients without progression(pattern a:60.61 ± 20.54 vs.52.51±11.89,p=0.017;pattern b:58.35 ± 15.79 vs.49.97 ± 14.62,p=0.008).After using logistic regression analysis,the levels were still significantly associated with disease progression(a3:p=0.037;a4:p=0.029;b4:p=0.006;b5:p=0.009).In the second part,the SEER database was used to verify the CTS5 model.The results showed that a total of 23168 hormonal receptor positive breast cancer patients were included,including 13686 postmenopausal and 9482 premenopausal patients.Taking CTS5 score as a continuous variable,it had significant positive correlation with poor prognosis beyond five years in both postmenopausal and premenopausal subgroups.Nevertheless,for HER2 positive postmenopausal patients,the model has less effective prognostic value on long-term BCSS[HR1.177(95%CI 0.960-1.443),p=0.117].Using CTS5 score as a categorical variable,HER2 negative patients with high-risk level revealed significant poor survival in terms of both BCSS and OS,irrespective of menopausal status.Our study showed the CTS5 model could be a useful prognostic tool for predict long-term survival in HR+/HER2-patients.Then a total of 147 hormone receptor positive/HER2 negative patients were enrolled and divided into three groups according to the CTS5 score.The distribution of IIRPCs in the three groups was similar to that in the first part,but the pattern c of IIRPCs in high-risk patients was less to find(low risk:medium risk:high risk=17.5%:22.6%:7.5%).Although the difference was not statistically significant,the adjusted absolute value of standardized residual in high-risk group was 1.9.There was no significant difference in IIRPCs levels among the three groups(F(2,53)=1.895,p=0.16 for pattern a and F(2,49)=1.601,p=0.21 for pattern b).Conclusion:The level of IIRPCs in peripheral blood of breast cancer patients with tumor recurrence or metastasis was higher than that of patients without disease progression.The individualized level of IIRPCs may become a potential indicator to monitoring the tumor load of breast cancer patients.According to analysis of SEER database,CTS5 model perform well in predicting the long-term prognosis of hormone receptor positive/HER2 negative patients regardless of menopause.The pattern c of IIRPCs in peripheral blood of high-risk patients according to CTS5 score was less to find,but there was no significant difference in the level of IIRPCs between each group.Patients with pattern c IIRPCs may have a higher risk of recurrence and metastasis,but the level of IIRPCs can not predict the risk of recurrence and metastasis.